What’s Coming Down the Pike

BDS
BDS Member Posts: 172
edited September 2014 in Kidney Cancer #1

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|htmlws-main-bb|dl1|sec3_lnk1&pLid=207936

 

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Comments

  • Texas_wedge
    Texas_wedge Member Posts: 2,798
    Information gathering

    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
    foxhd Member Posts: 3,181 Member

    Information gathering

    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.

    Good one

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

  • DMike
    DMike Member Posts: 259
    foxhd said:

    Good one

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

    Thanks

    Thanks BDS and Fox don't be bogartin'!

    --David

  • alice124
    alice124 Member Posts: 896 Member

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

  • garym
    garym Member Posts: 1,647
    Great work...

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

  • BDS
    BDS Member Posts: 172
    Bionomics BNC105P - Clincal Trial – First Post

    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
    Texas_wedge Member Posts: 2,798
    BDS said:

    Bionomics BNC105P - Clincal Trial – First Post

    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

     

    BNC105P

    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
    GSRon Member Posts: 1,303

    BNC105P

    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.

     

    More Hope..

    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
    Texas_wedge Member Posts: 2,798
    GSRon said:

    More Hope..

    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

    More hope

    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
    foxhd Member Posts: 3,181 Member

    More hope

    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.

    Major cool!

    enough said.

  • GSRon
    GSRon Member Posts: 1,303
    foxhd said:

    Major cool!

    enough said.

    Thanks

    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
    i_love_my_dad Member Posts: 20
    GSRon said:

    Thanks

    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

    finger crossed...

    Hope this may be the answer!

  • Mikeyswife
    Mikeyswife Member Posts: 31
    Thank for the Info

    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
    BDS Member Posts: 172
    Cabozantinib

    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
    BDS Member Posts: 172
    New Cancer Agent Debuts in Multiple Cancers

    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
    foxhd Member Posts: 3,181 Member
    BDS said:

    New Cancer Agent Debuts in Multiple Cancers

    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.

     

    I wish it was approved sooner

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

  • NanoSecond
    NanoSecond Member Posts: 653
    foxhd said:

    I wish it was approved sooner

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

    AACR Sessions on Immunology

    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
    Texas_wedge Member Posts: 2,798

    AACR Sessions on Immunology

    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

    Nivolumab research

    Neil, don't forget the special Fox pizza!

  • foxhd
    foxhd Member Posts: 3,181 Member

    Nivolumab research

    Neil, don't forget the special Fox pizza!

    Funny Tex

    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."

  • NanoSecond
    NanoSecond Member Posts: 653
    foxhd said:

    Funny Tex

    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."

    Extraneous factors

    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.