Help with clinical trials (RMC-6236 and it's variations)

I am so confused and scared. My husbands liver mets ( which had a great initial response and dissapeared on Gem/Abrax combo came back in less than 8 weeks) So it seems like the only way forward is to try clinical trials but the information on the clinicaltrials.gov page seems to be out of date. I called Revolution Medicine today and most of the trials that are listed as recruiting are closed. I don't know how to move forward? Do i just frantically call around every potential listing? Do we just wait until we maybe (?) get into a trial while his liver mets keep growing? This is even harder to navigate from here in Turkey with the time difference. Please let me know of your experiences.

Just for background info, "RAS" includes at least 3 subtypes (HRAS, NRAS, and KRAS), with KRAS being the most common in PDAC. In trial descriptions, you might see the descriptor "pan-RAS" which means it applies to more than one of these.

Each of those can be refined further; examples for KRAS include G12C, G12D, G12V, G13C, etc. In trial descriptions, you might see the descriptor G12X which means it applies to more than one of these.

You might also see descriptors "RAS(ON)" , "RAS(OFF)", or "RAS-ON" and "RAS-OFF" which describes drugs providing unique mechanisms of action relevant to very specific tumor mutations.

Also, if you're doing a search at clinicaltrials.gov, cancer.gov, or another site, you might not find pancreatic cancer listed as one of the diseases being targeted in a trial. Sometimes that's because the researchers are specifically not targeting PDAC. But in other cases, you may see "solid tumor" as one of the diseases or requirements. PDAC patients usually meet this criteria but often overlook it in their search.

Regarding previous lines of treatment: That is unique to every study. I tried getting into one of the RevMed Phase-1 trials combining RMC-6236 (pan RAS) combined with RMC-9805 (G12D) but didn't qualify because I'd already had too many lines of treatment. Some of the research teams are very specific about the market they're trying to get approval for, and such limitations sometimes ease that burden for them.

I wound up in a Phase-1 trial called MOONRAY of a new KRAS G12D inhibitor oral drug from Eli Lilly. Still too early to tell if it's working for me. Aside from vomiting, indigestion, and fatigue, the side effects are minor and manageable. This is a common trait of drugs with narrower targets than pan-RAS drugs.

Once you find an appropriate trial, there's still a lot of luck required to get accepted for one. One research nurse told me a LOT of it is being in the right place at the right time. I would add that sometimes "who you know" is also a factor. Applying (calling or emailing) blindly has not worked for me. I got both the RevMed consideration and the MOONRAY acceptance based on referrals from one of my many medical oncologists.

But as a general idea of what's out there, Click the link for my 37 search results from
https://clinicaltrials.gov/search
which searched just for the terms "KRAS G12D" and Status = Recruiting.

Sorry for the length, but I hope this is pan-Helpful. 😉

Cheers and good health,

--mm

P.S. The last paragraph in this blurb: https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-presents-updated-data-rmc-6236-monotherapy includes a few more interesting comments and insights about RevMed and their KRAS targeting drugs.

I have chased RMC-6236 all over the country but all trials are closed. The only exception might be Tango Therapeutics in Boston, but a specific mutation is required. It is worth a call to investigate.

Name: Maeve Waldron-Lynch, MD
Phone Number: 857-320-4899
Email: clinicaltrials@tangotx.com
https://www.clinicaltrials.gov/study/NCT06922591
IMO looking for the RMC-6236 trials on clinicaltrials.gov is a waste of time. Most of the information is outdated. Hang in there. We are all in the same boat.

@keepingoptimistic

Thanks. I did have correspondence with Meave but they're looking for MTAP deletion which my husband doesn't have. I have to say she was extremely generous with her time though. I also called Revolution Medicines and they directed me to another study which uses the same drug but we weren't eligible for that either unfortunately. Looking at other KRAS trials now.

@keepingoptimistic

Thanks. I did have correspondence with Meave but they're looking for MTAP deletion which my husband doesn't have. I have to say she was extremely generous with her time though. I also called Revolution Medicines and they directed me to another study which uses the same drug but we weren't eligible for that either unfortunately. Looking at other KRAS trials now.

What is the other Revolution Medicines trial that you mention?