Immunotherapy clinical trial!

kidclutch

I am starting a new thread because my dad is no longer going to be receiving docetaxel chemotherapy. His Foundation One genome testing returned this week. It showed ATM mutations, and he was referred to an immunotherapy clinical trial--a phase 2 trial where he will be receiving the trial drugs and not a placebo, to begin in two weeks. It will continue as long as there is clinical benefit (and discontinued if there is no clinical benefit).

The trial is testing the treatment of ATM mutated metastatic prostate cancer with avelumab (immunotherapy) and talazoparib (PARP inhibitor). Avelumab will be given via infusion twice monthly, and talazoparib is a daily pill. I can't seem to find much information for either drug in the treatment of prostate cancer, so would be grateful if any of you have seen anything or have any personal experience with either drug or drugs in their classes.

I will be happy to update throughout this process--here's hopin'!

VascodaGama

Here's hopin

Kid,

I share with you the desire for something good to happen. I wonder the name of the trial your dad will be doing.

These therapies involving Mabs in prostate cancer is quite new. There have been some trials since 2011 but only now they managed a consensual plan in treatments with the intent at cure. This is where the genetic test got its potential. It stratifies patients for a more targeted therapy. In your dad’s case, they found certain genes that are associated with ATM mutations linked to or provoking cancer. Findings of this type have been under investigation in breast cancer for already many years, which is a similar illness to prostate cancer (these share the same genes). Your dad’s clinical trial involve the work of two drugs, being the Talazoparib the monoclonal (the inhibitor) and the Avelumab the facilitator for the killing by the immune system.

The whole plan is to avoid that the protein PD-L1 created by the cancer gets together with the immune protein PD-1 which is a survival switch in all our cells. This switch must be turned off to let the cancerous cell to die.
We have discussed here before on Mabs but unfortunately all the exchanged superb opinions have been lost in the last outage of the forum (together with your initial thread). Mabs got worldwide attention since the last Nobel Prize on medicine (2018) given to Dr. James Allison and Dr. Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation.

I hope the trial is a success and manages to eliminate the bandit for good.

For those interested in knowing your dad’s story, they can check it in this link;

https://csn.cancer.org/node/319205

Here is an article on the successful of Monoclonal antibodies as a therapeutic approach in cancer;

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760278/

Here is a link to clinical trials using Avelumab;

https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/avelumab

 

Best wishes,

VGama

 

kidclutch

VascodaGama said:

Here's hopin

Kid,

I share with you the desire for something good to happen. I wonder the name of the trial your dad will be doing.

These therapies involving Mabs in prostate cancer is quite new. There have been some trials since 2011 but only now they managed a consensual plan in treatments with the intent at cure. This is where the genetic test got its potential. It stratifies patients for a more targeted therapy. In your dad’s case, they found certain genes that are associated with ATM mutations linked to or provoking cancer. Findings of this type have been under investigation in breast cancer for already many years, which is a similar illness to prostate cancer (these share the same genes). Your dad’s clinical trial involve the work of two drugs, being the Talazoparib the monoclonal (the inhibitor) and the Avelumab the facilitator for the killing by the immune system.

The whole plan is to avoid that the protein PD-L1 created by the cancer gets together with the immune protein PD-1 which is a survival switch in all our cells. This switch must be turned off to let the cancerous cell to die.
We have discussed here before on Mabs but unfortunately all the exchanged superb opinions have been lost in the last outage of the forum (together with your initial thread). Mabs got worldwide attention since the last Nobel Prize on medicine (2018) given to Dr. James Allison and Dr. Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation.

I hope the trial is a success and manages to eliminate the bandit for good.

For those interested in knowing your dad’s story, they can check it in this link;

https://csn.cancer.org/node/319205

Here is an article on the successful of Monoclonal antibodies as a therapeutic approach in cancer;

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760278/

Here is a link to clinical trials using Avelumab;

https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/avelumab

 

Best wishes,

VGama

 

Thanks so much!

Your explanation was certainly easier to read than the many studies about these drugs on the internet!

I have been occasionally speaking to Bryce Olson with Sequence Me— he had a similar diagnosis, received immunotherapy for his mutation, and has been thriving and advocating for genome sequence testing for patients ever since. He may take a look at my dad’s genome report and be able to tell me more. I will keep updating here as I learn more!

kidclutch

UPDATE

This update is a bit late, but I wanted to make sure I shared: The arm of the trial containing ATM mutated prostate cancer patients was closed out when all of the patients (including my dad) were not seeing any improvement and were dealing with toxicity from the trial drug combo (including increased pain, fatigue, etc.).

My dad will be moving onto a chemo trial called DORA next (after platelets come back up after a recent batch of radiation)--which will have two arms: docetaxel-only, and docetaxel plus radium-223. Hoping to be randomized into the docetaxel/radium-223 arm!

RE: the immunotherapy trial, though, the BRCA mutated patients were responding, so that's some positive news for some folks!

Max Former Hodgkins Stage 3

kidclutch said:

UPDATE

This update is a bit late, but I wanted to make sure I shared: The arm of the trial containing ATM mutated prostate cancer patients was closed out when all of the patients (including my dad) were not seeing any improvement and were dealing with toxicity from the trial drug combo (including increased pain, fatigue, etc.).

My dad will be moving onto a chemo trial called DORA next (after platelets come back up after a recent batch of radiation)--which will have two arms: docetaxel-only, and docetaxel plus radium-223. Hoping to be randomized into the docetaxel/radium-223 arm!

RE: the immunotherapy trial, though, the BRCA mutated patients were responding, so that's some positive news for some folks!

...mab

Monoclonal antibody drugs have been used agains blood cancers (leukemia, lymphoma) for about 20 years now. They are so common that they have taken the nickname of '...mab drugs,' from the two words Monoclonal Antibody. They operate by attaching a protean to a specific cancer cell, and as such are quite specific in what they will treat, but newer ones are being developed all the time.  A 'Mab' that works on one cancer cell is often later discovered to be effective against others, which is why these trials are so popular (the same thing is true of chemo drugs).  Mabs are occasionally confused with genetic immunology re-engineering therapy, or CAR-T, which they are not a form of.  CAR-T was begun as a salvage therapy against blood cancers also, and even for those is virtually brand new; who knows what it will someday be discovered to cure, but it is extremely promising, if outrageously expensive:  CAR-T, when it is used, costs about $1 million currently, whereas stem cell transplantation (STC) is as 'cheap' as $500,000 in some places now.  To my knowledge, SCT is used only against blood and bone cancers.

I received Rituxan (Rituximab) against my lymphoma in 2009-2010, and learned a bit about mabs.  They are not conventional 'chemos', since they  are not technically 'cytotoxic agents,' but rather work more indirectly.  Rituxan kills (indirectly) the CD-20 cell, which is common in many Lymphomas, but it is also used as a second-line pallative therapy against rheumatoid arthritis (RA), indicating the multiple uses these drugs are finding.  It is because they alter the immune system that TV commercials about them commonly warn that in some extremely rare cases they cause lymphomas to develop.

Mabs ordinarily are LESS SEVERE in side-effects than cytotoxic drugs. Few or none cause hair loss, for instance, and most do not cause nausea, either.  The most common side-effects are profound weakness and breathing issues, from cold-like symptoms, and they routinely skew liver and CBC results, but this is almost always temporary.   They are usually administered with IV Benadryl to prevent allergic reactions.

Docetaxel (often referred to as Taxotere) is a conventional chemo drug (a 'taxane').  As such, it has the full range of severe side-effects, usch as profound weakness, nausea (easily controlled to day with EMEND), and others. I have followed two friends through Taxotere treatments, as well as the "post-Taxane" drugs Zytiga and Jevtana.  Taxotere is (for decades now) the most common chemo against mPCa and also breast cancer.  It can be curative in combination with other drugs (such as TAC) against BCa, but is not regarded as curative against PCa, but is rather a pallative.  Joined with Radium, who knows.

'DORA' is of course derived from the words Docetaxel and Radium.  I pray that it become the 'next big thing,' and is effective for your father, kidclutch.

The following links are relevant, an obviously have some overlap with what Vasco provided....

US Clinical Trail for DORA:

https://clinicaltrials.gov/ct2/show/NCT03574571

General Avelumab information (note already in routine use against some U.T. cancers) :

http://chemocare.com/chemotherapy/drug-info/avelumab.aspx

May God save the Queen, and us all as well,

max