Anyone familiar with the clinical trial RMC-6236? Or how to enroll?

I was recently at the AWCR and ECOG-ACRIN oncology meetings and the reports on the phase II trial were very favorable. The RASolute 302 trial is underway in multiple sites including international sites and this drug is expected to receive expedited review when the study is complete for approval.

The management of RAS-related side effects with RMC-6236 appears to mirror the approach used for patients treated with EGFR inhibitors for metastatic colorectal cancer. This involves
antibiotic started as a preventive measure, typically cycling twice a day.

To address risk, topical steroids
and topical antibiotics are being used. Additionally, the study data indicates that dose modifications (interruptions or reductions) were used to manage side effects in some patients. Rash was the most common reason for dose reduction. Importantly, very few patients discontinued treatment due to Treatment Related Adverse Events (TRAEs) in the Phase 1 study.

Implications for Phase III:

It's likely that the experience from the Phase 1 trial, including the observed side effects and successful management strategies, will inform how side effects are monitored and managed in the ongoing Phase III RASolute 302 trial. The focus will likely remain on proactive management of common side effects like rash and gastrointestinal issues using similar supportive measures and dose adjustments as needed.

I was recently at the AWCR and ECOG-ACRIN oncology meetings and the reports on the phase II trial were very favorable. The RASolute 302 trial is underway in multiple sites including international sites and this drug is expected to receive expedited review when the study is complete for approval.

The management of RAS-related side effects with RMC-6236 appears to mirror the approach used for patients treated with EGFR inhibitors for metastatic colorectal cancer. This involves
antibiotic started as a preventive measure, typically cycling twice a day.

To address risk, topical steroids
and topical antibiotics are being used. Additionally, the study data indicates that dose modifications (interruptions or reductions) were used to manage side effects in some patients. Rash was the most common reason for dose reduction. Importantly, very few patients discontinued treatment due to Treatment Related Adverse Events (TRAEs) in the Phase 1 study.

Implications for Phase III:

It's likely that the experience from the Phase 1 trial, including the observed side effects and successful management strategies, will inform how side effects are monitored and managed in the ongoing Phase III RASolute 302 trial. The focus will likely remain on proactive management of common side effects like rash and gastrointestinal issues using similar supportive measures and dose adjustments as needed.

I was just denied entry last week into the combined 6236+9805 trial. The focus of this trial was on 9805 (KRAS G12D specific), and apparently the manufacturer is now focused on getting it approved as a second-line therapy. My rejection was because it would have been a third-line therapy for me.

What I've heard from two oncologists is that these drugs do have a good pedigree and track record so far.

My very limited understanding is that 6236 is sort of "broad-spectrum" targeting KRAS G12x ("x" meaning multiple subtypes) whereas 9805 specifically targets KRAS G12D. As a result of its broad targeting, 6236 may cause more side effects than the more narrowly focused 9805.

Good luck to everyone navigating the clinical trial obstacle course!

RMC-6236 is the furthest along in development of the KRAS inhibitors by Revolution Medicine. ThenGDA has a provision where trials can be shortened when the clinical evidence is overwhelmingly supports the efficacy of a drug. There is also a provision in trials with a control and test arm and the participants in the test arm are receiving overwhelming benefit, those in the control arm will get moved over to receiving the drug as it would be unethical to deprive them of its benefit.

Could you try and get into a trial of just the 6236? City of Hope in Irvine (CA) is hoping to get this soon. If you could travel for initial setup you could continue your care back in Florida. Dr.Kasi at Hope will be in charge of that trial. Or there’s the Naliri chemo available which I’ll be starting next week unless radiologist were to set up my SBRT first.

@mnewland99 , Thanks for the info. Do you have the NCT trial # for the one at COH?

The only ones I'm aware of w/ RMC-6236 are either Phase 3 (randomized; not going there) or in combination w/ other SoC chemo drugs that I haven't already had.

Even though 6236 is an oral med I could take at home, I don't think I could get into a trial at COH without frequent travel back to CA since they want to measure absorption rates and blood concentrations -- I doubt I could find a local lab/provider willing, capable, or approved to do the tests that study requires.

The only SoC drug I haven't tried is Onivyde (the new nano-liposomal irinotecan). I asked my onc today if I should switch to that as a bridge until I qualify for a trial. I was advised not to, because the likely failure/progression on another line of therapy would jeopardize my chances of getting into a trial with more promise.

I'll be getting tested for expression of CLDN18.2 soon, and checking into other studies. There are some KRAS G12D trials with drugs other than RevMed's.

@mnewland99 , Thanks for the info. Do you have the NCT trial # for the one at COH?

The only ones I'm aware of w/ RMC-6236 are either Phase 3 (randomized; not going there) or in combination w/ other SoC chemo drugs that I haven't already had.

Even though 6236 is an oral med I could take at home, I don't think I could get into a trial at COH without frequent travel back to CA since they want to measure absorption rates and blood concentrations -- I doubt I could find a local lab/provider willing, capable, or approved to do the tests that study requires.

The only SoC drug I haven't tried is Onivyde (the new nano-liposomal irinotecan). I asked my onc today if I should switch to that as a bridge until I qualify for a trial. I was advised not to, because the likely failure/progression on another line of therapy would jeopardize my chances of getting into a trial with more promise.

I'll be getting tested for expression of CLDN18.2 soon, and checking into other studies. There are some KRAS G12D trials with drugs other than RevMed's.

@mnewland99 , Thanks for the info. Do you have the NCT trial # for the one at COH?

The only ones I'm aware of w/ RMC-6236 are either Phase 3 (randomized; not going there) or in combination w/ other SoC chemo drugs that I haven't already had.

Even though 6236 is an oral med I could take at home, I don't think I could get into a trial at COH without frequent travel back to CA since they want to measure absorption rates and blood concentrations -- I doubt I could find a local lab/provider willing, capable, or approved to do the tests that study requires.

The only SoC drug I haven't tried is Onivyde (the new nano-liposomal irinotecan). I asked my onc today if I should switch to that as a bridge until I qualify for a trial. I was advised not to, because the likely failure/progression on another line of therapy would jeopardize my chances of getting into a trial with more promise.

I'll be getting tested for expression of CLDN18.2 soon, and checking into other studies. There are some KRAS G12D trials with drugs other than RevMed's.