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What’s Coming Down the Pike

BDS's picture
BDS
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Joined: Aug 2012

There are many new treatments for RCC currently in Clinical Trials around the world. Below is my compilation of what I believe are the most promising treatments that are on the horizon for RCC. Hopefully, these new drugs/treatments will receive FDA approval within the next 1-3 years. Each drug I mention contains snippets of information that I have copied from the Internet. - BDS      

 

 

Tivozanib (Aveo Pharmaceuticals) is a potent pan-VEGF receptor tyrosine kinase inhibitor. The biological activity of tivozanib seems to outstand that of other VEGF tyrosine kinase inhibitors. In Phase I studies, observed side effects are generally mild, with hypertension being the most common adverse event. In single-agent Phase II and III studies in patients with advanced or metastatic renal cell carcinoma, tivozanib has demonstrated convincing clinical activity.

In a statement, Aveo said that the FDA has accepted the company’s NDA, submitted in September, for tivozanib as a treatment for advanced renal cell carcinoma (RCC), or kidney cancer. The FDA’s review of the candidate is expected to be completed by July 28, 2013, the company said. The NDA includes results of the global Phase 3 trial, TIVO-1, of 517 patients with advanced RCC. The study showed that tivozanib was the first product to demonstrate more than one year of progression-free survival for patients who had never taken medication for the disease before. In a head-to-head comparison, AVEO’s drug candidate bested Nexavar, the current standard of care, made by Onyx Pharmaceuticals.

 

AVEO Oncology  Astellas Pharma Inc. today announced that new clinical data on tivozanib, an investigational agent for the treatment of metastatic renal cell carcinoma (mRCC), will be presented at the 2013 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), taking place February 14-16 2013 in Orlando, Florida Presenter: Robert Motzer, M.D.   Date & Time: Saturday, February 16, 2013; 6:45-7:55am

WebLink:http://www.aveooncology.com/our-product-candidates/tivozanib/renal-cell-carcinoma/

Search Youtube for Videos:

 

BMS-936558/Nivolumab (Bristol-Myers Squibb):  It is proposed that the anti-PD-1 treatments currently being investigated work against the cancer cells by blocking them from binding to and activating PD-1. This helps the body reactivate the immune response and fight back against the cancer.

Web Links: http://www.bmsanti-pd-1drugresearchstudies.com/index.aspx

Search Youtube for Videos:

 

BNC-105P: There is an Australian company called Bionomics that is conducting clinical trials of a new promising drug called BNC105 or BNC105P.  BNC105 is a vascular disrupting agent that shuts down the blood supply to solid tumors.

Web Link: http://www.bionomics.com.au/index.php )

Search Youtube for Videos:

 

IMA901 vaccine: Completed a European multi-centerphase 2 clinical trial in renal cell carcinoma in Q4 2009. 68 patients with advanced renal cell carcinoma were treated and highly encouraging overall survival rates were observed in the treated patients, significantly improving on the data seen from market-leading drugs in previous studies. Furthermore, IMA901 showed an excellent safety profile. Based on these very encouraging results and on discussions with regulatory bodies in the US (FDA) and Europe (EMA), immatics initiated a pivotal, randomized, controlled phase 3 study that, presenting positive outcomes could soon lead to the market approval of IMA901.

 

Web Links: http://www.immatics.com/index.php

                    http://www.immatics.com/index.php?action=download&id=571

Search Youtube for Videos:

 

TVAX Biomedical is a clinical stage drug development company advancing its novel targeted cell-based immunotherapy for the treatment of cancer.

TVI-Kidney-1 is being evaluated for the treatment of kidney cancer and targets stage IV renal cell carcinoma.As with TVI-Brain-1, this drug candidate is supported by positive Phase 2 clinical data, as well as extensive preclinical and Phase 1 safety studies.  Based on these supportive data, TVAX has been authorized by the United States Food and Drug Administration (FDA) to conduct pivotal Phase 3 trials for TVI-Kidney-1 to support the therapy’s potential FDA approval.  The company has prioritized the TVI-Brain-1 program at this time, but intends to initiate the TVI-Kidney-1 pivotal Phase 3 trial in the near future.

Web Links: http://www..com/index.shtltvaxbiomemdical 

Argos Therapeutics

AGS-003 is an investigational, fully personalized, cancer immunotherapy being evaluated in a phase 3 clinical study in combination with targeted drug therapy for the treatment of metastatic renal cell carcinoma (mRCC).

To make AGS-003, a small tumor sample is obtained during the initial, standard surgery (nephrectomy). Following recovery from surgery, a blood donation procedure (leukapheresis) is performed to collect a certain type of blood cell which is required to make powerful dendritic cells. Once these elements are combined, up to 5 years of treatment is made for each patient.

Where AGS-003 Fits:

Adding AGS-003 to targeted drug therapy may represent an important advancement in the treatment of advanced kidney cancer. In a previous clinical trial, AGS-003 was safely added to a commonly used targeted therapy and appeared to trigger an immune response which helped patients fight their cancer.

Web Link: http://adaptkidneycancer.com/

 

AGS-16C3F

Not Sure Who Makes this Drug: AGS-16C3F is an antibody-drug conjugate. It is composed of an antibody which binds to a specific receptor on cancer cells. Once there, a chemotherapy drug that is bound to the antibody can kill the cancer cell. AGS-16C3F is given intravenously (by vein).

Weblink: http://www.mskcc.org/cancer-care/trial/12-162

 

 

 

Exelixis Inc

 

Cabozantinib (Exelixis Inc.) is an inhibitor of both VEGFR2 and c-Met, both of which promote angiogenesis. 25 patients were evaluated, all of whom had prior therapies for kidney cancer, mostly VEGF or mTOR inhibitors. This was an experienced group as close to half of the patients had three or more prior therapies. For example, 14 of the 25 had previously taken sunitnib (Sutent). The dosage was 140 mg/daily, which was previously determined to be the maximum tolerated dose (MTD). Other studies have used 40 mg to 140 mg, with the lower dose showing efficacy in prostate cancer. Exelixis, the biotech company that developed the drug, will consider dose reduction in the future for RCC. 

 

Response


The progression-free survival (pfs) for the 25 patients was 14.7 months. With respect to tumor shrinkage, 21 patients were evaluated, and, based on RECIST criteria, of those, 7 had a partial response (>30% shrinkage), 13 had stable disease, and one had progression. In total, 19 of the 21 evaluated patients had some shrinkage, although one had progressive disease due to new lesions.  

 

Based on prostate trial data, cabozantinib has demonstrated significant efficacy in reducing or eliminating bone lesions. There were four rcc patients with bone lesions at baseline, two with pain. The pain resolved for both and one has continued to be pain-free for 73 weeks. One patient did develop new bone lesions. According to Exelixis, in addition to cabozantinib’s effect on osteoblasts and osteoclasts, an anti-tumor effect was also noticed in the bone lesions. It will be interesting to see further elucidation of this since, as compared with Zometa, which is an agent that has been used successfully to treat bone metastases, it is still unclear if there is an anti-tumor effect. 

 

What stands out in this trial is the response rate, specifically the pfs of 14.7 months and some tumor shrinkage in 19 of the 21 evaluated patients for a patient mix that was heavily pre-treated. For example, of the 7 patients who showed partial tumor response (> 30% shrinkage), 4 of them had four or more prior treatments. The best pfs in current therapies is about a year, and this is mostly for treatment-naïve patients. The axitinib-sorafenib second-line trial (with one prior therapy) yielded a pfs of 6.7 months and 4.7 months for axitinib and sorafenib, respectively. Additionally, the patients on this trial were all in the intermediate and poor risk categories. Most trials have patients who have good and intermediate risk for recurrence. Cabozantinib also demonstrated efficacy against bone lesions, following its similar history with prostate cancer. The drug also seems to be well-tolerated without the significant hypertension and possibly concomitant heart issues found in other tyrosine kinase inhibitors.  

Although the numbers are small, there doesn’t seem to be a relationship between number of prior therapies and response to cabozantinib. In other words, it doesn’t matter how many priors you’ve had, you still have a possibility of tumor response to cabozantinib.

 

Weblink: http://www.exelixis.com/

 

Note – (I could be wrong on this But…) Only a Phase 1 trial has been completed with Cabozantinib for RCC.   From what I can currently determine the company (Exelixis) is not vigorously pursuing a Phase 2 clinical trial.  I cannot find any mention of it on ClinicalTrials.gov only on Exelixis website where it is in a status of “Not Yet Recruiting”.  - BDS

 

 

Acceleron Pharma

Dalantercept: February 5, 2013 – Acceleron Pharma, Inc., a biopharmaceutical company developing protein therapeutics for cancer and orphan diseases, announced the initiation of a phase 2 study of dalantercept, a novel angiogenesis inhibitor that targets the activin receptor-like kinase 1 (ALK1) pathway.  The phase 2 study is a two-part, randomized study of dalantercept in combination with axitinib (Inlyta®, Pfizer), a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, to treat patients with metastatic renal cell carcinoma (RCC).  Acceleron, its partners, and collaborators have now initiated seven phase 2 studies across three of Acceleron’s programs – dalantercept (ACE-041), sotatercept (ACE-011), and ACE-536 – since November of 2012.

“Many patients with renal cell carcinoma respond to treatment with a VEGF inhibitor yet their disease subsequently progresses,” said Michael B. Atkins, M.D., Deputy Director, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center. “We are optimistic that combining two therapies with distinct anti-angiogenesis mechanisms, a VEGF inhibitor and dalantercept, an ALK1 signaling inhibitor, can provide a more effective and durable antitumor response in these patients.”

Weblink: http://www.acceleronpharma.com/

 

Interesting Articles:

 

Rice-Cell Cocktail Tough on Cancer Cells, Nice to Normal Cells

Weblink: .com/articles/rice-cells-nice-to-normal-cellscell-cocktail-tough-ncer-on-cahttp://www.newswise 

Marijuana and Cancer: Scientists Find Cannabis Compound Stops Metastasis In Aggressive Cancers

 

Weblink:  http://www.huffingtonpost.com/2012/09/19/marijuana-and-cancer_n_1898208.html?icid=maing-grid10%7Chtmlws-main-bb%7Cdl1%7Csec3_lnk1%26pLid%3D207936

 

Texas_wedge's picture
Texas_wedge
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Nice one BDS - the more information gathering like this we can do, the better. 

There are more than this but that's a pretty encouraging list.

So far, the front-runners there are nivolumab and cabozantinib. Aveo's share price took a knock when the results turned out to be disappointing, which is a shame since we need to see more players in the game and it would be good to see smaller ones like them thriving.

It's also a shame when somewhat deceitful claims are made.  When they say that Nexavar is 'the current standard of care', one is tempted to say that that is years out-of-date in the age of Sutent, Votrient and Inlyta, which have/are supplanting Nexavar in general use for RCC. 

It's also a meaningful question to ask 'care for what?'  Now that it's increasingly recognised that in RCC we don't have different sub-types, but totally different diseases that just happen to be in the same organ, with different metabolic pathways, we have to ask which of these different diseases a drug applies to.

Please keep up the good work, BDS and be well.

foxhd's picture
foxhd
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DS. Thanx. I've got the nivolumab part in control. I may have to take the marijuana claim a bit more proactively.

DMike's picture
DMike
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Thanks BDS and Fox don't be bogartin'!

--David

alice124's picture
alice124
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Great job BDS. Will hold in my favorites file for quick reference. Appreciate your compilation.

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sblairc
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This information does not specifically mention the chromophobe renal cell carcinoma but it is referencing the research by the Cancer Genome Atlas which just revealed breakthrough information into the biology of chromophobe RCC. I've posted about this on another thread if you search for it but wanted to add it here and bump up this post, of course. Hope for all in this research, I believe. I put the last emphasis in bold myself. 

Written by: 
Philips GK, Atkins MB.   Are you the author? 
Department of Oncology, Georgetown-Lombardi Comprehensive Cancer Center and Division of Hematology/Oncology, Medstar Georgetown University Hospital, Washington, DC.

The vascular endothelial growth factor (VEGF) pathway blockers and mammalian target of rapamycin (mTOR) inhibitors have dramatically improved the treatment options and outcome for patients with advanced renal cell carcinoma (RCC).

However, because the vast majority of patients will still succumb to their disease, novel treatment approaches are still necessary. Efforts to identify novel therapeutic target treatments are focused on better understanding unique aspects of tumor cell biology guided the Cancer Genome Atlas analyses and the interaction of the tumor with its microenvironment. Areas of promising investigation include a) the identification of mechanisms of acquired resistance to VEGF pathway inhibition and developing agents targeting these in combination with VEGF receptor (VEGFR) pathway blockade; b) the identification of novel therapeutic targets, particularly for patients with VEGF pathway blocker refractory disease; and c) the development of novel immunotherapies, particularly those involving checkpoint inhibitors used alone or in combination with other immunotherapies of VEGF pathway blockers. Specific targets or agents of interest include angiopoietins (trebaninib), c-Met (cabozantinib), activin receptor-like kinase-1 (ALK-1; dalantercept), interleukin (IL)-8, and HDM2 for acquired resistance to VEGF pathway inhibition; hypoxia inducible factor-2 alpha (HIF-2 alpha), TORC1/2, and the Hippo pathway for novel targets, and PD1 and PDL1 antibodies given either alone or in combination with other checkpoint inhibitors, other immunotherapies, or VEGF pathway blockers for novel immunotherapies. In addition, the application of genetic, immunologic, or other biomarkers developed in the context of this research has the potential to select patients with specific tumor types for therapy targeted to specific vulnerabilities within the tumor or tumor microenvironment. Together, these developments should enable the transition to a new era of rational and more effective therapy for patients with advanced RCC.

Written by: 
Philips GK, Atkins MB.   Are you the author? 
Department of Oncology, Georgetown-Lombardi Comprehensive Cancer Center and Division of Hematology/Oncology, Medstar Georgetown University Hospital, Washington, DC.

Reference: Am Soc Clin Oncol Educ Book. 2014:e222-7. 
doi: 10.14694/EdBook_AM.2014.34.e222

PubMed Abstract
PMID: 24857106

UroToday.com Investigative Urology Section

NanoSecond's picture
NanoSecond
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However, as regards the new Chromophobe study (and likely true of all cancers), the key part of that research was the finding that the roll of the Mitochondria and mDNA (Mitochondrial DNA) needs to be considered and may be far more important.

The Cancer Genome Atlas has been primarily concerned (up to now) with the Nucleus and nuclear DNA.  The above paper makes no mention of yet to be introduced metabolic therapies (which are certainly novel) for this reason.

garym's picture
garym
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Posts like this should be premanently pinned tp the top of the page so the newbies can see it first thing!

BDS's picture
BDS
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Bionomics BNC105P - Clincal Trial – First Post

 

Below is the first post I have found of someone in the BNC105P (Bionomics) in Combination with Everolimus (Afinitor) Clinical trail for Metastatic Clear Cell Renal Cell Carcinoma. BNC105P is a new drug that is neither a VEGF or mTOR inhibitor but a vascular disrupting agent that shuts down the blood supply to solid tumors. So far this drug looks encouraging. – BDS

 

  On Wed, Mar 27, 2013 at 8:24 AM, Mary Prazma  wrote:

 

> After 3 rounds (84days) on Afinitor and the trial drug BNC-105P (6

> infusions) I am happy to report a 16% reduction in mets in my lungs and

> other adrenal gland, stability in one in the pancreas and maybe an "almost

> can't see" shrinkage on the other pancreas met.

> My doctor says Afinitor is usually a stabilizing drug so it may be the

> BNC-105P that is doing the shrinkage!  Makes all those trips and sticks

> worth it.

> Of course, he also says I only have a little bit of cancer, but to me

> that's like being a little bit pregnant.

> Prayers and best wishes for everyone.

> Mary Prazma

 

 

BNC105 - vascular targeting agent

BNC105 was developed using Bionomics' proprietary MultiCore technology used to create novel compounds.

The mechanism of action of BNC105 is similar to that of any VDA. VDAs act by cutting the blood supply to tumours, thereby depleting them of oxygen and nutrients required for survival. Such an approach to treating cancer is much more effective than other conventional treatments, as killing a single blood vessel can eliminate thousands of tumour cells.

Compared to other VDAs BNC105 has a higher therapeutic index, which means that a bigger window exists between one effective dose and a dose at which toxic effects are observed. Being more selective for blood vessels of tumours renders the enhanced therapeutic index to BNC105.

In addition to being a VDA, BNC105 is a cytotoxic agent or tubulin polymerisation inhibitor. BNC105 targets only the cancer cells and acts as a toxic agent to only those cells and not the normal cells. It can be combined with other treatments such as radiation therapy to eliminate tumours.

Another unique feature of BNC105 is that it is cleared from normal cells quickly and is retained within the tumours. This "lock-in" effect has provided better treatment response to the drug and also showed fewer side-effects in clinical trials.

http://www.biospectrumasia.com/biospectrum/news/155399/bionomics-update-bnc105-trials

 

Texas_wedge's picture
Texas_wedge
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The trial is under a top gun - Thomas Hutson - and is running in numerous sites in the States and also in Australia and Singapore.   It's due to end in June of this year, so we may not have very long to wait before getting some idea of its success rate.

BDS, please keep it coming, but a word to the wise - in copying the quote above, you're breaking the rules of both that site and this one.

 

GSRon's picture
GSRon
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Hi All..!  Check this out... it may be a long while before it is out.. but... perhaps a cure..??

http://med.stanford.edu/ism/2012/march/cd47.html

I will be at Stanford next week and will ask questions...

Be Well..!

Ron

Texas_wedge's picture
Texas_wedge
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Glad you thought to bring this up here Ron - it's causing what I think is thoroughly justified excitement on various other forums and sites.

CD47  -    keep a close eye on this one folks and anyone who can take part in a trial  -  I envy you.

foxhd's picture
foxhd
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enough said.

GSRon's picture
GSRon
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I am so pleased that I am (for once) able to offer something TO the group... you all have taught me ever so much..!!  Let's hope and pray this may be THE answer..!

Be Well..!

Ron

i_love_my_dad
Posts: 20
Joined: Jan 2013

Hope this may be the answer!

Mikeyswife
Posts: 31
Joined: Mar 2013

This is a great site with great people!  Thanks for all the information.  I have been reading everything I can get my hands on for the last nine weeks since my husband's diagnosis.  With stage 3 grade 4 30% sarcomatoid, I know we need to be prepared.  Surgeon released him on Thursday.  On to Dr. Rini at the Cleveland Clinic on April 10th.  Hopefully the scans will still be clear!

My prayers and thoughts are with you all.

BDS's picture
BDS
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It looks like there is going to be a Phase II trial with cabozantinib vs sunitinib starting soon. However, it will be limited to treatment naïve patients – BDS

https://www.calgb.org/Public/publications/calgabs/2013/Winter-Vol-3-No-2-2013.pdf

BDS's picture
BDS
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Below is a nice article about nivolumab/BMS-936558. The most interesting point of the article for me was the prediction given that nivolumab/BMS-936558 may be FDA approved by 2015. - BDS  

New Cancer Agent Debuts in Multiple Cancers

'Living Therapy' May Last for 'Many Years'

Nick Mulcahy

Apr 08, 2013

WASHINGTON, DC — In a noteworthy moment in the history of cancer drug development, phase 3 clinical trials of an experimental agent are simultaneously underway in 3 different cancer types.

Trials of the investigational immunotherapy nivolumab (Bristol-Myers Squibb) have begun in melanoma, renal cell carcinoma, and nonsmall-cell lung cancer, said Suzanne Topalian, MD, here at the annual meeting of the American Association for Cancer Research (AACR) 104th Annual Meeting. She is from the Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland.

The simultaneous trials of a single investigational agent in so many different cancers "may be unprecedented," Dr. Topalian told Medscape Medical News in an interview.

The phase 3 trials are an outgrowth of the positive results seen in phase 1 trials of nivolumab, which was previously called BMS-936558 and MDX-1106. The agent is a monoclonal antibody that neutralizes the programmed death 1 (PD-1) protein, an element of tumors that enables them to evade their nemesis, the immune system.

Nivolumab was hailed as the next big thing in cancer treatment last year after early data indicated that it had durable tumor response rates of 20% to 30% in multiple cancers. In the words of one expert, the agent had "broken the ceiling" of durable tumor response rates of 10% to 15% that has existed for cancer immunotherapies over the past 30 years.

That an immunotherapy — and not some other type of cancer treatment — should be making such an auspicious debut in phase 3 trials is not an accident, Dr. Topalian noted.

"In many ways, the adaptive immune system comprised of T-cells and antibodies is an ideal anticancer agent," she told the audience at a plenary session.

Dr. Topalian challenged the prevailing wisdom in cancer research.

"The current dogma is that cancer is a genetic disease," she explained, acknowledging that individual tumors contain hundreds of mutations and alterations in signaling pathways, which are the basis of the personalized medicine approach.

But the genetic model is highly problematic, she argued. The problem of resistance to targeted therapies "has its limitations," she noted. "Blocking one pathway can lead to the emergence of another," she explained.

An "alternative viewpoint" proposed by Dr. Topalian is that "cancer is an immunologic disorder."

Immunotherapy is the "common denominator" that "takes advantage of the fact that many of the mutations of cancer can be specifically recognized and targeted by the immune system." Furthermore, "the immune system can adapt and evolve as the cancer evolves," she said.

Dr. Topalian showed a timeline of the identification of the PD-1 gene and the development of an anti-PD-1 therapy (Nat Immunol. 2012;13:1129-1132). The timeline, which was not created by her research team, projects US Food and Drug Administration approval of anti-PD-1 therapies by 2015.

"If nivolumab is approved, it would be so inspiring and motivating for the field of immunology," said Priyanka Agharkar, a predoctoral trainee from the Department of Cell Stress Biology at the Roswell Park Cancer Institute in Buffalo, New York. Aside from sipuleucel-T (Provenge) for prostate cancer and ipilimumab (Yervoy) for melanoma, "there is very little approved in terms of immunotherapies for cancer," she told Medscape Medical News.

There is now plenty of competition in the field of anti-PD-1 agents and complementary anti-PDL1 agents. In fact, Genentech, Amplimmune/GSK, CureTech, Merck, and MedImmune all have drug development programs.

Proof From 3 Patients That the Immune System Has "Memory"

The quality that makes the immune system "different from all other cancer therapies" is that the immune system has "memory," said Dr. Topalian.

To support her assertion, she showed treatment and response timelines for 3 of 39 patients treated with nivolumab in the first-in-human trials for melanoma, renal cell carcinoma, nonsmall-cell lung cancer, prostate cancer, and colorectal cancer.

The 3 patients had objective responses for a "very long time" after a single course of treatment with nivolumab, she reported.

A patient with colorectal cancer had a complete response after a few months of treatment, which has remained into year 4 after initiation of treatment.

A patient with kidney cancer had a partial response after a few months of treatment; the tumor continued to shrink and a complete response was seen in year 3 after treatment. The patient has maintained the response into year 4.

null

A melanoma patient had a partial response and was taken off treatment after a few months. In year 3 after trial enrollment, that patient had lymph node metastases and resumed treatment, but has achieved an ongoing partial response into year 4.

In addition, in a follow-up phase 1 trial of nivolumab, durable tumor regressions were seen in approximately 300 patients with lung cancer, melanoma, and kidney cancer, and regressions persisted even after the drug was discontinued.

These results are "compatible" with the idea that the immune system has a memory, said Dr. Topalian.

"This is actually a living therapy that stays with the host, potentially for years," she noted.

She explained that the duration of the effect could be similar to childhood vaccines for infectious diseases, and the resulting immunity might even last a lifetime.

Dr. Topalian reports a financial relationship with Bristol-Myers Squibb.

American Association for Cancer Research (AACR) 104th Annual Meeting. Presented April 7, 2013.

 

foxhd's picture
foxhd
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Great information BDS. I hope that one day my case will be a scientific write up.

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NanoSecond
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Hi Fox,

I think it just may.  I actually attended the entire AACR Annual Meeting this past week here in DC.  It started on Saturday and only ended yesterday.  I was fortunate to hear many fascinating presentations regarding the latest research on immune-based therapies as well as on several other cutting-edge topics under rigorous discussion at the show.

Your favorable response to using this PD1-blocking agent is, no doubt, more than of passing interest.  Many of the papers presented in the immunology track were about ways to extend the "success" of these new drugs  - i.e. how to get more patients to a CR (complete response) or PR (partial response).

So, some quick questions for you.  What additional information, if any, are they tracking about you?  In particular, are they interested in your fitness regime? Are they following any of your lifestyle habits (such as diet, or sleep cycle, or at least beer consumption)?

Keep up the great work - may I add my voice to the rest of us who praise your infectious inspriring attitude.

 

-N

Texas_wedge's picture
Texas_wedge
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Neil, don't forget the special Fox pizza!

foxhd's picture
foxhd
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Neil, I don't know. But I am going to ask about this next visit. What I think I know is that to have been choosen to be accepted in the study, these issues were addressed.

1st, I had to have clear cell ca. 2. Surgery was ok but I had to be treatment naive. ie no other drug treatments. 3. So much blood work. I bet 40-50 vials were taken during the first couple months. I believe they were looking for some genetic markers. DNA was tested. 4. I had to have no other major health issues. 5. Biopsies taken from a met before and after first treatment. 6. Attitude and fitness level. I don't remember any particular questions that were asked as if they were being read from a prepared format but maybe. 7. and scans, and scans, and scans.

I do believe that these trials admit some people that can ensure success of the study. Also some that will fail. Having radiation for the bone mets was ok. Now, I only get 2-4 vials of blood work taken. Basic cbc and I imagine mdx blood levels and who knows what else. Scans are now every 12 weeks. I feel good about that.

I don't know what is going on behind the scenes, but now you've got me thinking. I also remember being told early blood work was specially sent out of the clinic for testing. Probably Bristol Meyer Squib. Now? I don't know.  Regarding alcohol consumption, I was asked how much beer I drink and I said PRN. Which is medical talk for "as needed."

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NanoSecond
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Thanks Fox.  Do give this some thought if you have a chance.  Going to the AACR conference was literally mind-numbing.  It is going to take me months to decipher what I have seen and learned.  For example, the "book" of Proceedings listing all the papers being presented was 1523 pages long in extremely teeny-tiny typeset.  But that's not all.  At the start of the show I was then handed a "Proceedings Supplement: Late-Breaking Abstracts" that was another 159 pages long.  Just to go through and collate all the papers that might touch on topics directly related to RCC (or of personal interest) will take me daze, er, days.

However, there were some extremely tantalyzing papers (that, incidentally, were all heavily attended) regarding such topics as:

- Cancer and Metabolism: Metabolic considerations and Novel Cancer Therapies; Whole Body Metabolism; Metabolism and Signaling; etc. - All of these and related topics were my personal area of interest and that interest is apparently shared by countless other researchers.  That really surprised me.

- Immunology

- TME - Tumor Micro-Environment (i.e. the support given to tumors and mets by the surrounding "normal" tissues

- Drug resistance and how to extend effectiveness.

- "Liquid Biopsies" (deciphering what the tumor or mets are doing by analyzing Circulating Tumor Cells or tumor DNA (not in any cells) in the blood.

- Tumor and/or metastases evolution; latent metastases; dormant tumor cells, etc.

- Future Anti-Cancer Targets

 

Regardless, if one were to attempt to take an overall view of where current research is going it consistently pointed to thinking outside of the genome, beyond the nucleus, beyond the cytoplasm, outside of the abnormal cells and into the surrounding environment and then on to the entire system.  That is why it would be invaluable to figure out what "external" factors might be contributing to one person's success (yours) on a given therapy while it may fail for someone else.

 

TerriNick
Posts: 43
Joined: Mar 2013

Hi Neil

Sorry to be dim but I am still new to all this. What do you mean when you talk about 'complete response' and 'partial response' please? Do any of these mean that the cancer is beaten into submission and remission happens or is that just a pipe dream of mine?

 

NanoSecond's picture
NanoSecond
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Joined: Oct 2012

Hi Terrie,

No need to apologize - we are all constantly learning new concepts and acronyms as part of our initiation process into the posh and exclusive kidney cancer club.  Pretty soon you will be ready to learn the secret handshake as well...

The holy grail of any therapy would be to get a complete response - i.e. No visible Evidence of Disease, usually referred to as NED.  But more often the response is less than complete - perhaps the mets just stabilize (do not grow but do not shrink either).  Of perhaps some mets shrink but others are not effected.

There is a rigorous set of criteria to meet called "RECIST".  Here is a link that quickly outlines the criteria:

http://imaging.cancer.gov/clinicaltrials/imaging

From that link:

RECIST criteria are a voluntary, international standard, and are not an NCI standard. They are based on a simplification of former methods (WHO, ECOG) and based on measurable disease, i.e., the presence of at least one measurable lesion.

RECIST criteria offer a simplified, conservative, extraction of imaging data for wide application in clinical trials. They presume that linear measures are an adequate substitute for 2-D methods and registers four response categories:

  • CR (complete response) = disappearance of all target lesions
  • PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions
  • PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions
  • SD (stable disease) = small changes that do not meet above criteria

Plans call for improving on RECIST methodology by developing and validating clinical trial-acceptable methods and standards to incorporate:

  • volumetric (3D) anatomical imaging
  • dynamic contrast imaging
  • functional (molecular) imaging

If successful, the use of medical image data as a surrogate endpoint in clinical trials could lead to:

  • Smaller clinical trials with fewer patients
  • Earlier go/no decisions on drug compounds
  • Faster regulatory approval for new drugs
  • Earlier use in clinical care
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Texas_wedge
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The last few lines of your post are very promising, Neil.  May not get as far as n=1 though?  :)

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foxhd
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Always up on top of things. I like smart people. Saves me alot of work. Thanks.

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LOL Fox, you are too funny!  Heck, i like 'em too.  It is a pity they get picked on in school!  ;)

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Terri... NED does happen for some.  And if you are like Fox here, it happens BIG TIME!  Read up on his story if you haven't.  It is very encouraging.  Lots of new meds here now and down he pipeline!  It is all good!

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Mind boggling stuff Neil. Thank you for trying to break it down for the rest of us.

In reading  different  articles and updates on treatment and new drugs, I often see reference to medical conferences. And to be honest, I don't know the difference between one conference and another.  I mean is this AACR the Masters of Cancer research meetings? Should one conference be given more credibility than another? There's more and more infomation becoming available and increasingly difficult to determine what is the best information. Given you have 1700+ pages of info to decipher, I'm guessing this was a biggie, and one of the premiere conferences on topic. In your opinion, wihich annual meetings/conferences do you consider the most enlightening?

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Hi Alice,

I am chagrined that you would ask my opinion - because I am such a newcomer to this entire field.  Believe it or not everything I "know" about RCC, nutrition, diet, cancer (and normal) cell metabolism, etc. I have only learned since I was declared "stage IV" this past July. My formal education is not in any medical field - my degree is in Electrical Engineering. Although I did once take a course in Organic Chemistry.

Regardless, I have always depended on educating myself.  In my approach I try not to take anything for granted or to let the opinions of others sway me away from potential controversy.  That, for example, is why I have disregarded "experts" who have told me not to waste my time investigating whether or not dietary changes could be of any help in fighting cancer.

In the same spirit I decided to attend the AACR Annual Meeting because I wanted to go right to the top and hear the latest research from the experts themselves.  The downside to this is that I have still have so much more to learn, decipher, and digest. I definitely do not recommend this kind of approach for most other folks.  It is kind of like those immersive techniques for learning a new foreign language by refraining from speaking in one's native tongue.  At first this is totally disorienting and very difficult.  But slowly things do begin to make some sense.

This is a long roundabout way of admiting that I have not been to any other conferences (as yet) and so I can't answer your question as to which is the best or which I recommend. However, I have seen some excellent online reviews of several Kidney Cancer Symposiums - and I would definitely plan to put those on any calendar.

I actually did not realize that the AACR Annual Meeting featured full length and ongoing Patient Advocacy sessions (which were not quite as technical as they were geared to layman).  To be honest, I knew very little (prior to this show) of what I was getting into.  Once I was there I was immediately swept up in the enormity of it all.  But there was some fun stuff too. The Opening Ceremony and Award Presentations featured the "AACR Distinguished Public Service Award" being bestowed on Katie Couric.  Her (at times) quite humorous acceptance speech was followed by several interesting lectures such as those by Dr. Siddhartha Mukherjee (author of "Emporer of Maladies") and Dr. Suzanne Topalian - whose presentation on Immunology merited some press coverage reported elsewhere on this site.  The entire conference was suspended for a few hours on Tuesday so that the entire audience could attend the "Rally for Medical Research" protest (featuring participation by over 200 other organizations). This event was designed to send a powerful message to Congress to stop reducing the funding of the NIH.  It was hosted by Cokie Roberts of NPR fame.  Most absurdly, I ended up being interviewed on a local TV station covering the event.

Such are the weird perks of having renal cancer.  :)

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While your forte may be in the dietary aspects of fighting RCC, you're quickly becoming one of our house experts Neil. And we'll take all the expertise we can get. We appreciate all that you share.

 

(BTW, is there a link to your interview still out there? Would love to see it.)

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...Seem to be lost in cyberspace.  I never got to see it - but at least my wife and daughter did.

I have been unable to find that interview posted anywhere.  It was done by Ch. 4 - WRC-TV - the local NBC affiliate in Washington, DC.

There is full YouTube coverage of the actual rally though.  Just google "Rally for Medical Research".  It was a very impressive turnout.

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of Neil and BDS and so many of you posting for all that you share on the various sites.  Science is not my strength so it is hard for me to slog through the detail and decide what I need to know and what is better left to the experts.  I am tremendously grateful for those of you that can decipher it all and explain it so the rest of us can understand as well.  Rick (an engineer) is usually quite good at it, but like me, has had his head down for a few months just trying to survive and recover.  Feels like we've been in a fog since mid-December.  This thread is a nice way to catch up on what's new and what to be on the watch for.  Thanks for putting it all in one place!

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This is excellent information BDS! You certainly are using your situation to the fullest by keeping on top of treatments helping all of us!  I too wish the Nivo.... would be approved much sooner. I also thought i heard it was used for gyno cancers as well.  I think finally they are onto something by working with the immune system.  Thanks for the new info... keeping on going!  

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Abstract

Purpose: VB-111 is an anti-angiogenic agent consisting of a non-replicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a fas-chimera transgene in angiogenic endothelial cells. In a phase I dose-escalation study pharmacokinetics, pharmacodynamics, safety and efficacy of a single dose of VB-111 in patients with advanced solid tumors was evaluated.

Experimental design: VB-111 was administered as a single intravenous infusion at escalating doses from 1x1010 (cohort 1) to 1x1013 (cohort 7) viral particles (VPs) in successive cohorts. Assessments included pharmacokinetic and pharmacodynamic profiles, tumor response and overall survival.

Results: Thirty three patients were enrolled. VB-111 was safe and well tolerated; selflimited fever and chills were seen at doses above 3x1011 VPs. Transgene expression was not detected in blood, but was detected in an aspirate from a subcutaneous metastasis after treatment. One patient with papillary thyroid carcinoma had partial response.

Conclusions: VB-111 was safe and well tolerated in patients with advanced metastatic cancer at a single administration of up to 1x1013 VPs. Evidence of transgene expression in tumor tissue and tumor response was observed. 

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Scientists Develop Functioning Artificial Animal Kidney

In other news: Punching microscopic holes in tumors could be effective cancer treatment.

 By Erinn Connor, Everyday Health Staff Writer

Scientists have successfully grown an animal kidney in a lab and seen it work on a living animal, providing hope for the thousands of people in need of a kidney transplant.

Researchers at Harvard and Massachusetts General Hospital created a replacement kidney that, when transplanted into a rat, immediately started creating urine just like a normal kidney. Though the artificial kidney could not live up to the full function of a natural kidney, experts say it’s a promising move towards replacement kidneys.

“These results are really quite impressive,” said Dr. Mala Sachdeva, a kidney specialist who was not involved in the research. “The transplanted tissue was actually functional.” Though she cautioned “it’s very early to get our hopes up too high. A lot more work needs to be done.”

The bioengineered kidneys were created by stripping rat kidneys of their “living cells” and then repopulated what was left behind with kidney cells from newborn rats, along with human cells used to replace the lining of kidney blood vessels.

In the U.S. nearly 1 million people have end-stage kidney disease, and there are currently more than 95,000 people on the organ donor waiting list, according to the United Network for Organ Sharing.

Poking Holes in Tumors is New "Least-Invasive" Treatment

Researchers presented a new way to destroy cancerous tumors without damaging healthy tissue — using “minimally invasive” needles placed on the tumors.

Findings presented at the Society of Interventional Radiology’s Annual Scientific Meeting showed that irreversible electroportation, or IRE, lets doctors destroy tumors with the electrical pulses delivered by the needles using the “least-invasive treatments available,” said lead author Constantinos Sofocleous, an interventional radiologist at Memorial Sloan-Kettering Cancer Center, in a statement.

IRE drills microscopic holes in tumors that cause them to die when placed exactly, but also limit damage to surrounding blood vessels and nerves. Though further research is needed, scientists believe patients with liver, lung and pancreatic cancer will benefit the most from this procedure.

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Tivozanib has just been turned down by the FDA on the basis of the inadequacy of the trial comparing it with sorafenib.

This looked to me like a racing certainty on the data.  A pity that Aveo made such a pathetic attempt.  It will inevitably be quite a while before there's any chance of this drug coming to market and it may well be overtaken by history as better options like nivolumab, cabozantinib and others in the pipeline get there first.

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Hi All... Well a pal of mine has ACC  (Adenoid Cystic Carcinoma).  And I was trying to help him, as he was told surgery was the only hope.. WRONG..!  There are a bunch of Chemo drugs that possibly can give him more time before surgery, etc..   So, when looking some of them up, I see some familiar drugs and some new Clinical Trials for drugs I do not know of....  And when I read the info... some of them also mention Kidney Cancer... so below is the link...  I have not singled out the Kidney related ones... but it can make for interesting reading... as some of the issues mentioned may be similar or appropriate for some of us..  As always.. I am no doctor...

http://www.clinicaltrials.gov/ct2/results?term=Adenoid+Cystic+Carcinoma&Search=Search

And this link... go to page 6, and you will see both new and familiar drugs, and their performance for ACC... again different than RCC but I think it is good reading.. Note the Sutent has an awesome Stabil Disease of 92%... however there is a caveat on this one.. but still interesting.   Also of note is that there are some combination drugs that have better results...  I see that for RCC we may see a similar trend, combine two or more drugs and get a better result..

I hope this gives some insite and hope...

Ron

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UCLA's Dr. Antoni Ribas discusses PD1 and PD-L1 targeted cancer drugs

            http://www.youtube.com/watch?v=f3md01ReYVA

Dr Motzer of Memorial Sloan-Kettering Cancer Center discusses Tivozanib. Too bad the FDA's Oncologic Drugs Advisory Committee (ODAC) voted its disapproval. This I believe is truly a mistake. - BDS

            http://www.youtube.com/watch?v=KPqcCPlMwWA&feature=player_embedded

            http://www.youtube.com/watch?v=ndbbonUOcx8&feature=player_embedded  

 

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Hi All..!!

Today I was at Stanford for a follow up.. and I remembered to ask about CD47.  (Note that I did not see my Oncologist, I saw another one today... it was a busy day there.).  So when I asked about CD 47, her eyes lit up..!!  She went on how everyone is excited about it.. and she confirmed what the general news stories are saying..  However the people testing is still in the waiting stage from the FDA...  not sure when the first human trials will be... But I did say that I was interested..  I will not get back to Stanford for about 7 weeks.. but will try to remember to ask for an update..

Ron

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foxhd
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I just watched those videos and a few more related to it. Good stuff. I'm lucky to be a part of it.

i_love_my_dad
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Here is some information I find about BNC105. Sorry if this is redundant information. 

It mentioned that in a phase 2 study that 8 our of 12 patients achieved stable desease, (7 received treatment for more than 11.25 months and 1 has been on the drug for 17.25months.) Although I do not know whether the patients were pretreated or not.  

 

http://www.biospectrumasia.com/biospectrum/news/155399/bionomics-update-bnc105-trials#.UZ3H7JPIFAU

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Anti-CD47 antibody may offer new route to successful cancer vaccination

May 21, 2013 by Christopher Vaughan in Cancer

(Medical Xpress)—Scientists at the School of Medicine have shown that their previously identified therapeutic approach to fight cancer via immune cells called macrophages also prompts the disease-fighting killer T cells to attack the cancer.

The research, published online May 20 in the Proceedings of the National Academy of Sciences, demonstrates that the approach may be a promising strategy for creating custom cancer vaccines.

Various researchers have been working over the years to create vaccines against cancer, but the resulting vaccines have not been highly effective. Current approaches to developing the vaccines rely on using immune cells called dendritic cells to introduce cancer protein fragments to T cells—a process known as antigen presentation. The hope has been that the process would stimulate the body's T cells to identify cancer cells as diseased or damaged and target them for elimination. However, this process often only modestly activates the most potent cancer-fighting kind of T cell, called killer T cells or CD8+ T cells.

The Stanford team discovered that there was another viable vaccine approach, using the macrophage pathway to program killer T cells against cancer. Irving Weissman, MD, professor of pathology and of developmental biology, and his team previously showed that nearly all cancers use the molecule CD47 as a "don't-eat-me" signal to escape from being eaten and eliminated by macrophages. The researchers found that anti-CD47 antibodies, which can block the "don't-eat-me" signal and enable macrophages to engulf cancer cells, eliminated or inhibited the growth of various blood cancers and solid tumors.

In the new study, the Stanford team showed that after engulfing the cancer cells, the macrophages presented pieces of the cancer to CD8+ T cells, which, in addition to attacking cancer, are also potent attackers of virally infected or damaged cells. As a result, the CD8+ T cells were activated to attack the cancer cells on their own. "It was completely unexpected that CD8+ T cells would be mobilized when macrophages engulfed the cancer cells in the presence of CD47-blocking antibodies," said MD/PhD student Diane Tseng, the lead author of the study. Following engulfment of cancer cells, macrophages activate T cells to mobilize their own immune attack against cancer, she said.

The Stanford group plans to start human clinical trials of the anti-CD47 cancer therapy in 2014. The new research provides hope that the therapy will cause the immune system to wage a two-pronged attack on cancer—through both macrophages and T cells. The approach may also give physicians early indicators of how the treatment is working in patients. "Monitoring T-cell parameters in patients receiving anti-CD47 antibody may help us identify the immunological signatures that tell us whether patients are responding to therapy," said co-author Jens Volkmer, MD, an instructor at the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

The research revives interest in an aspect of macrophages that has been neglected for decades: their role in presenting antigens to T cells. For many years, researchers have focused on the dendritic cell as the main antigen-presenting cell, and have generally believed that macrophages specialize in degrading antigens rather presenting them. This research shows that macrophages can be effective at antigen presentation and are powerful initiators of the CD8+T cell response.

The fact that T cells become involved in fighting cancer as a result of CD47-blocking antibody therapy could have important clinical implications. The antibody might be used as a personalized cancer vaccine allowing T cells to recognize the unique molecular markers on an individual patient's cancer. "Because T cells are sensitized to attack a patient's particular cancer, the administration of CD47-blocking antibodies in a sense could act as a personalized vaccination against that cancer," Tseng added.  

                                 

Below is a link to the Stanford School of Medicine website containing a webpage and video about CD47. BDS

http://stemcell.stanford.edu/CD47/

 

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GSRon
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Hi All..!!  I was at Stanford on 9-5-13 and asked about CD47 again.  Yes looks like the date for the 1st trial has been moved to mid-2014.  But it also states there may be a trial in the U.K.  So my U.K. pals please note..!  The link seems to have the best info, thanks BDS..!   I will continue to ask about it.. as this really sounds promising..!  Oh yes, and just me asking about it, got several smiles..  All the people I see at Stanford are very pleased about the possibility...  Hang on folks..!!  Please be able to hang on... Ron   Oh yes, go to the link below, then watch the video.. I think it is very impressive..!

http://stemcell.stanford.edu/CD47/

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Promising data for cancer vaccine INTUVAX™ in the treatment of kidney cancer

Immunicum AB (publ) presents a status update with promising data from an ongoing clinical phase I/II-study of the cancer vaccine INTUVAX™ in the treatment of metastatic renal cell carcinoma. Two patients with poor prognosis have thus far shown an average survival of about 11 months, which can be compared to the expected median survival of 5 months. 

Immunicum AB (publ), a Swedish listed company developing therapeutic cancer vaccines, initiated a clinical phase I/II-study in renal cell carcinoma with its leading cancer vaccine INTUVAX™ in February 2012. On May 21, Immunicum’s CEO gives an update of clinical data at Avanza Bank's Stock Exchange Day.

The clinical trial will include a total of 12 patients with metastatic renal cell carcinoma of which 9 have been treated to date. The treatment consists of two intratumoral injections/vaccinations with INTUVAX™ every two weeks, after which the cancerous kidney is surgically removed.

All treated patients are still alive and injection of INTUVAX™ has not had a negative impact on patients' general condition and no serious side effects have been reported. No patients have so far been considered in need of additional treatment with established kidney cancer drugs.

One of the patients belonging to the subgroup with poor prognosis has so far demonstrated a progression-free survival exceeding 8 months, compared with an expected progression-free survival of approximately 2.5 months in untreated patients in a comparable prognosis group.

- Although we still cannot be sure of the vaccine efficacy, the data that has been gathered so far is looking promising", says CEO Jamal El-Mosleh.  INTUVAX™ also seems to be free from the troublesome side effects such as extreme fatigue, nausea, vomiting, painful mouth ulcers and hypertension, which are frequent in the treatment with established drugs for kidney cancer.

For the four patients treated with a higher dose of INTUVAX™, a statistically significant (P <0.01) immunological effect, associated with vaccination, has been observed in the form of a transient decrease in the number of "natural killer cells" (NK cells) in the blood. This suggests that NK cells are recruited to the vaccination site. Furthermore, immunohistological studies revealed a massive infiltration of potentially cytotoxic T cells (CD8 + T cells) in 3 out of 7 treated renal tumors (surgically removed in connection with nephrectomy). However, no increased infiltration of CD8 + cells were observed in the surrounding healthy kidney tissue, indicating that infiltration, and the immune response, is tumor-specific. The infiltration of CD8 + T cells in a resected metastasis has also been studied where a significant infiltration of these cells in the tumor tissue has been noted, indicating that the immune response has effect throughout the entire body and not just locally in vaccinated tumors.

- These immunological findings correspond well with the expected mechanism of action, says Immunicum’s Chief Scientific Officer and founder, Associate Professor Alex Karlsson-Parra.

Immunicum’s patented vaccine is based on over 30 years of research in the field of transplantation immunology and activates the body's own immune system to attack harmful substances like tumor cells.

Web Link

http://www.immunicum.com/

 

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Orlando, Fla.—In patients with aggressive metastatic renal cell carcinoma (RCC), combining the standard therapy of sunitinib (Sutent, Pfizer) with an experimental fully personalized immunotherapy called AGS-003 (Argos Therapeutics) can double expected progression-free survival (PFS) and overall survival. These results come from a Phase II trial presented at the 2013 ASCO Genitourinary Cancers Symposium (abstract 348).

“We have encouraging clinical and immunologic responses that have been observed and correlated with prolonged overall survival,” said Robert Figlin, MD, the director of the Division of Hematology/Oncology at Cedars-Sinai’s Samuel Oschin Comprehensive Cancer Institute in Los Angeles, who presented the study.

To produce AGS-003, monocytes are isolated from RCC patients during a single leukapheresis procedure and differentiated into dendritic cells. These cells are loaded with antigen-encoding RNA amplified from the patient’s tumor and injected into the patient. Each production run of AGS-003 generates up to five years of treatment for each patient. The immunotherapy stimulates the proliferation of central and effector memory cytotoxic T lymphocytes for a durable immune response.

In the study, 21 patients with newly diagnosed, advanced-stage, unfavorable-risk RCC received one cycle of sunitinib and then five doses of AGS-003 three weeks apart and AGS-003 quarterly until disease progression. Sunitinib also was given until disease progression. The only adverse events (AEs) that were attributed to AGS-003 were injection-site erythema, which occurred in 33.3% of patients, and injection-site induration, which occurred in 23.8% of patients. No grade 3/4 AEs were related to the immunotherapy, and there was no evidence of emergent autoimmune disease.

The median PFS was 11.2 months, and Dr. Figlin pointed out that the median PFS for patients in a similar population who received sunitinib monotherapy would be approximately six months. The median overall survival of the study patients is 30.2 months, roughly twice that expected in a similar population of patients receiving sunitinib monotherapy.

Investigators are planning the Phase III ADAPT trial to compare AGS-003 plus standard therapy with standard therapy alone in newly diagnosed, advanced RCC.

Leonard Gomella, MD, the chair of the Department of Urology at Jefferson University Hospitals in Philadelphia, said the data on AGS-003 was “very encouraging and will need to be confirmed in a larger number of patients.”

—Kate O’Rourke

Web Article:

http://www.clinicaloncology.com/ViewArticle.aspx?d=Solid%2BTumors&d_id=148&i=May+2013&i_id=960&a_id=23268

 

You know it is hard to keep up with all the new developments in renal cell carcinoma but I am trying. - BDS  Smile

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Texas_wedge
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You know it is hard to keep up with all the new developments in renal cell carcinoma but I am trying. - BDS

 

And a damned fine job you're making of it, BDS, for which we're all greatly indebted to you!!!

Apart from the actual content itself, the sheer fact that so much promising work is being carried out is a huge boost to the morale for everyone here.

one putt
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BDS  Thanks for keeping all of us updated. It gives all of us great hope for the future.

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BDS
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U.S. drugmakers cheer 'speed lane' for breakthrough therapies

 

By Toni Clarke | Reuters 

 

WASHINGTON (Reuters) - A new regulatory pathway could shave years off the traditional drug approval process in the United States, according to some companies whose drugs have been given "breakthrough therapy" designation by the U.S. Food and Drug Administration.

 

Speaking at a briefing in Washington to raise awareness of the drug review process, Dr. Jay Siegel, head of global regulatory affairs at Johnson & Johnson, said he expects two years to be knocked off the time it would typically take the FDA to review ibrutinib, the company's experimental cancer drug.

 

To be granted breakthrough designation, an experimental drug must show early indication of clinical improvement over existing therapies, even if the clinical trial is small. It might apply, for example, to a new type of cancer drug that shows strong early promise.

 

J&J's ibrutinib, which it is developing with Pharmacyclics Inc, would be the first in a class of oral medicines that block a protein known as Bruton's tyrosine kinase. It is being developed for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and for patients with mantle cell lymphoma, both cancers of the blood.

 

Dr. Jeffrey Leiden, the chief executive of Vertex Pharmaceuticals Inc, who also spoke at the briefing and whose cystic fibrosis drug Kalydeco was approved under the designation, said his company's experience working with the FDA was dramatically different from the normal drug approval process.

 

Under breakthrough designation, he said, "everything is on the table" for discussion in order to move the process along as quickly as possible. Communications that might typically take weeks and months, under the breakthrough pathway take minutes.

 

"We pick up the phone and talk in real time," Leiden said. "It makes the process immeasurably smoother."

 

The breakthrough pathway was spearheaded by Friends of Cancer Research, a patient advocacy organization. It received bipartisan support in Congress and was signed into law in July 2012. As of July 12, the FDA had received 67 requests for breakthrough designation. It had granted 24 and denied 18.

 

Dr. Janet Woodcock, director of the FDA's drugs division, said during the discussion that the breakthrough pathway was designed to accommodate new science, particularly targeted therapies that may work in people with certain genetic mutations. She noted that just because the review process is speeded up there is no guarantee of approval.

 

In the 1990s, she said, the agency was not seeing drugs whose promise could be detected in early clinical trials.

 

"We didn't see these therapies in Phase I or II where you said 'bingo,' you've got a likely winner," she said.

 

Still, there are challenges associated with speeding up a drug's development timeline. For one thing, other nations might not be willing to approve the products based on the FDA's more flexible clinical trial standards under the breakthrough designation.

 

"Our hope is that foreign regulators will catch up," Siegel said.

 

Moreover, he said, it is not clear that insurers will pay for drugs if the data do not show improved survival or other clear benefit they are used to seeing when drugs are approved. One task, he said is to figure out "how to bring payors on board."

 

The panelists did not discuss what happens once a drug reaches the market under the breakthrough designation.

 

Under a separate pathway known as "accelerated approval" drugs may be approved based on a so-called surrogate endpoint - a measure, such as tumor shrinkage - that might reasonably be expected to confer a clinical benefit such as improved survival.

 

Companies that win approval for a product under the accelerated approval process are required subsequently to prove through further clinical trials that the surrogate measure does in fact correlate with improved survival or a reduction in disease symptoms.

 

"A discussion on this topic is reckless if it doesn't discuss the next stage after the drug reaches the market," said Sidney Wolfe, co-founder and senior adviser to Public Citizen's Health Research Group, a watchdog organization that has frequently criticized the FDA for approving, or failing to withdraw, drugs it considers unsafe.

 

Woodcock said the FDA is now working to develop a mechanism to speed the development of breakthrough diagnostics that can be used in conjunction with new drugs to help identify which patients will respond to a particular therapy.

 

(Reporting by Toni Clarke; Editing by Ros Krasny and Lisa Shumaker)

 

i_love_my_dad
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http://shearlingsplowed.blogspot.com/2013/04/merck-oncology-candidate-granted.html

This drug is also granted as "breakthrough" and it is now chasing Nivolumab. Will patients benefit from the catching up game? I hope so!!!!

 

Here are some other clinical trials I've been watching, BDS.

1. Dovitinib is against FGFR pathway, and the clinical results show its effectiveness in heavily pretreated patients. Since it targets a differernt pathway, I am hoping that it can extend life in the true sense. 
 
The article below tells us sth about FGFR pathway.
 
2. Another one is Gemcitabine + Capecitabine,the article below summarizes several experiments that have been conducted. These two drugs are already FDA approved, right? 
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