Clinical Trials: they are not designed only to be a “last resort”

Yes,I am interested. My husband has liver lesions and I would like to get him on a clinical trial
Can you help me
Thank yo

È possibile avere informazioni su dove si può effettuare sperimentazione RM9805?
Sono Italiana
Grazie per una gentile risposta

Ciao, sono Italiana volevo sapere di più sulla tua sperimentazione e come sta andando.
Io conosco la sperimentazione RMC-6236 ma qui dall'italia è difficile accedervi.

English translation
Hi, I'm Italian and I wanted to know more about your trial and how it's going.
I know about the RMC-6236 trial but here in Italy it's difficult to access it.

Lots of helpful new discoveries are happening to increase the understanding of why pancreatic cancer is so tough to treat. One or more of the clinical trials that spin out of this basic research are going to push the therapy options for pancreatic cancer forward in completely new directions that both work better and are easier to tolerate than the standard combination chemotherapy regimens that have been the only options to date.

I posted about this particular drug in another thread - which just had major news announced this week on July 15th, 2024. RMC-6236 from Revolution Medicines is about to go into Phase III testing in the second half of 2024. The trial will be accepting patients - with and without specific RAS mutations - who are available to enroll as a second line (2L) treatment option after having taken an initial chemo regimen.

RAS mutations are present in the vast majority of pancreatic cancer patients (92%!), but have not been "druggable" as a treatment pathway until very recently. Having a background in my past life in clinical drug development and being the husband of a late stage, newly diagnosed PCan patient, this is really exciting stuff!

Per the investor update on RMC-6236 a few days ago:

"RMC-6236 is the first targeted investigational drug designed to directly inhibit all major forms of oncogenic RAS, the major drivers of PDAC (pancreatic ductal adenocarcinoma)."

"RMC-6236 has shown compelling anti-tumor activity and a favorable safety profile in a broad population of patients with previously treated PDAC, and has potential to become an important new treatment option."

"Extensive efforts are ongoing toward launching RASolute 302, a global, randomized Phase 3 clinical trial comparing RMC-6236 to chemotherapy as 2L treatment of patients with metastatic PDAC."

Yes! Go to Revolution Medicines website and see recent slides from their investor call held 7/15. I have begun a trial that includes RMC 6236 and their KRAS G12D specific drug, RMC 9805. Stage IV, working on a liver tumor. Excited -and glad to be off chemo for a bit. 🤞it works!! For all of us.

"Ciao, sono Italiana volevo sapere di più sulla tua sperimentazione e come sta andando.
Io conosco la sperimentazione RMC-6236 ma qui dall'italia è difficile accedervi."

Translation:

Hi, I'm Italian, I wanted to know more about your experimentation and how it's going.
I know about the RMC-6236 trial but here in Italy it is difficult to access it.

Clinical trial sites for Revolution Medicine’s RMC-9805 small molecule drug targeting KRAS G12D variant is in a phase Ib trial at Yale University in New Haven Connecticut. Depending on results of this dose escalation study, it could result in an expanded phase II study. Sites will be listed by doing a search on clinicaltrials.gov and if offered in any EU country, search for the E.U. Clinical Trials database.

You may be more interested in RMC-6236, a pan-KRAS marker that just reported on 15 July exciting results of its phase II trial which is a significant breakthrough. This trial covered many sub-variants of KRAS including G12D. Revolution Medicine announced plans for a phase III study expected to be announced in September. It will be posted on their website and clinicaltrials.gov website. If the expanded trial includes countries outside the U.S., the trial listing will have this information.

I siti di sperimentazione clinica per il farmaco a piccola molecola RMC-9805 di Revolution Medicine mirato alla variante KRAS G12D sono in uno studio di fase Ib presso la Yale University di New Haven, nel Connecticut. A seconda dei risultati di questo studio di incremento della dose, potrebbe risultare in uno studio di fase II ampliato. I siti verranno elencati effettuando una ricerca su clinictrials.gov e, se offerti in qualsiasi paese dell'UE, cercare l'E.U. Banca dati degli studi clinici.

Potresti essere più interessato a RMC-6236, un marcatore pan-KRAS che ha appena riportato il 15 luglio risultati entusiasmanti del suo studio di fase II che rappresenta una svolta significativa. Questo studio ha riguardato molte sottovarianti di KRAS, incluso G12D. Revolution Medicine ha annunciato i piani per uno studio di fase III che dovrebbe essere annunciato a settembre. Sarà pubblicato sul loro sito Web e sul sito Web Clinicaltrials.gov. Se la prova estesa include paesi al di fuori degli Stati Uniti, l'elenco delle prove conterrà queste informazioni.

A small addendum to stage IV survivor notes-data has now been published on the 9805 drug that shows the effective dose rate and tumor shrinkage/stability in colon and Pcan patients.
Of course, not all patients have KRAS G12d mutation so the positive news on 6236 is wonderful and hopeful. The trials are being held in at least 6 sites across the US. I don’t see that a site has been qualified internationally yet. You can find the trial sites by looking at Revolution Medicines website.
Also clinical trials.gov

Convince my husbands oncologist to apply. He was accepted but then couple days later said the tumours on his liver had yo be 2cm and his are 1.5 cm. Disappointing But that was 1st step as a biopsy would have yo be tested to see if it was the mutations they were looking for. Is that the case with all trials??

I just wanted to add a caveat that, although clinical trials are not "only intended to be a last resort," they should not be taken lightly.

In some trials, you may receive the standard of care or the standard of care plus a trial drug/therapy. For other trials you have to be completely off all other drugs/therapies to test only the trial drug by itself.

I've been Stage-IV PDAC for almost 2 years now, but with pretty good control over everything. After 15 months on SoC therapy (Gem+Abrax+Cis), we started seeing signs and hints (but not definitive evidence) of drug resistance. My neuropathy was getting worse, my bone marrow and bloodwork were taking a beating, I had a break in my work schedule, and an opportunity to participate in a very promising, cutting-edge trial.

Two independent oncologists agreed it was good timing and the right thing to do, so I jumped through all the hoops and was accepted into the trial.

The trial required at least 4 weeks washout from any previous chemo, followed by 7 weeks in the treatment / observation phase. Insurance issues, travel, and other logistics added about 2 weeks, making a 13-week (3-month) period off chemo before I got final results.

Unfortunately, the treatment did no good at all. Cancer grew and spread during that time period instead. We were able to revert to and resume my previous chemo within two weeks of those final results, but the tumor growth didn't just stop on a dime. The primary tumor continued to advance, and within two weeks, landed me in the hospital with an intestinal blockage where I am today, awaiting placement of a stent to open the blockage so I can eat again.

---

In hindsight, a few months before the hints of drug resistance developed, one of my oncologists said I was responding so surprisingly well to the GAC for so long that it would border on unethical to go off it for a trial of unknown efficacy. Although I did reach the point where the trial made sense, the "unknown efficacy" part (which turned out to be zero) was a real disappointment.

Phase-1 trials offer a lot of innovative and promising treatments, but their primary purpose (along with testing effectiveness) is to identify dose-limiting toxicities and recommended dosing for Phase-2 trials. Phase-2 seems to be a sweet spot somewhere between Phase-1 (being a guinea pig) and Phase-3 (risk of placebo).

I thought this was important enough to share. I hope my lesson from this is a benefit to someone!