RMC-6236 for Pancreatic Cancer

(RASolute 302 Trial)

Recruiting in Palo Alto (17 mi)

+28 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Revolution Medicines, Inc.

Must not be taking: RAS-targeted therapy

Disqualifiers: CNS metastases, Major surgery, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to standard(s) of care (SOC) treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug RMC-6236 for pancreatic cancer?

Research shows that targeting KRAS mutations, which are common in pancreatic cancer, can be effective. Similar drugs that inhibit pathways like RAF/MEK/ERK and PI3K/AKT have shown promise in reducing tumor growth in pancreatic cancer models. ^{1 2 3 4 5}

Is RMC-6236 safe for humans?

Preliminary results from phase I trials indicate that RMC-6236, a pan-RAS inhibitor, is safe and shows promising signs of antitumor activity. ^{1 4 6 7 8}

What makes the drug RMC-6236 unique for treating pancreatic cancer?

RMC-6236 is unique because it is a pan-RAS inhibitor, meaning it targets multiple forms of the RAS protein, which is often mutated in pancreatic cancer. This approach is different from other treatments that typically focus on specific mutations like KRASG12C, potentially offering broader effectiveness against various RAS mutations. ^{1 4 7 9 10}

Research Team

Study Director

Principal Investigator

Revolution Medicines

Eligibility Criteria

This trial is for patients with advanced pancreatic cancer (PDAC) who have already undergone treatment. Participants should be adults with a confirmed diagnosis and measurable disease, able to perform daily activities with relative independence.

Inclusion Criteria

Measurable disease per RECIST 1.1

My pancreatic cancer has spread and was confirmed by lab tests.

I am over 18 and have agreed to participate.

Exclusion Criteria

I have no conditions that affect my ability to take or absorb medications.

I have been treated with drugs targeting RAS proteins.

I cannot or do not want to follow the study's required visits or procedures.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either RMC-6236 or Investigator's choice of standard of care chemotherapy

Up to approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 3 years

Treatment Details

Interventions

• RMC-6236 (RAS Inhibitor)

Trial Overview The study tests RMC-6236, a new potential drug targeting specific cancer pathways, against standard chemotherapy treatments like 5-fluorouracil, irinotecan, nab-paclitaxel, gemcitabine, oxaliplatin and liposomal irinotecan combined with leucovorin.

Participant Groups

Group I: RMC-6236 Experimental Treatment 1 Intervention

Study drug

Group II: Investigator's choice of standard of care therapy Active Control 7 Interventions

Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments: * Gemcitabine and nab-paclitaxel (GnP) * Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX) * Liposomal irinotecan (Nal-IRI + 5-FU/LV) * Oxaliplatin, leucovorin and 5-FU IV (FOLFOX)

Who Is Running the Clinical Trial?

Revolution Medicines, Inc.

Lead Sponsor

Trials

14

Recruited

4,500+

Findings from Research

KRAS mutations play a crucial role in pancreatic ductal adenocarcinoma (PDAC), and the study found that KRAS inhibitors BI-3406 and sotorasib, alone or in combination with other inhibitors, showed cytotoxic effects on specific PDAC cell lines.

The combination of BI-3406 with trametinib and buparlisib enhanced anti-tumor efficacy in certain cell lines, indicating that targeting KRAS and its downstream pathways could be a promising therapeutic strategy for PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of KRAS, MEK and PI3K Demonstrate Synergistic Anti-Tumor Effects in Pancreatic Ductal Adenocarcinoma Cell Lines. Ma, Y., Schulz, B., Trakooljul, N., et al.[2022]

Current treatments for pancreatic cancer are inadequate, highlighting the need for new approaches.

Recent research into the genetic mechanisms of pancreatic cancer has led to the development of targeted molecular medicines that focus on specific signaling pathways, such as RAS-MAPK, PI3K-AKT-mTOR, and hedgehog pathways, which may offer new therapeutic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular targeting therapy for pancreatic cancer: current knowledge and perspectives from bench to bedside. Furukawa, T.[2021]

Phase I trials of RMC-6236, a pan-RAS inhibitor, and HRS-4642, a KRASG12D inhibitor, have shown that both drugs are safe for use and exhibit promising antitumor activity.

These findings highlight the potential of developing RAS-targeted therapies beyond just KRASG12C, indicating a growing interest in more comprehensive treatment options for cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drugging RAS: Moving Beyond KRASG12C. [2023]

In a phase 2 clinical trial involving 137 patients with metastatic pancreatic cancer, the combination of selumetinib and MK-2206 did not improve overall survival compared to the standard mFOLFOX treatment, with median survival times of 3.9 months versus 6.7 months, respectively.

The experimental treatment resulted in more severe side effects, with 39 patients experiencing grade 3 or higher toxic effects compared to 23 in the mFOLFOX group, leading to a higher rate of treatment discontinuation due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy: SWOG S1115 Study Randomized Clinical Trial. Chung, V., McDonough, S., Philip, PA., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Multiple mechanisms involved in a low concentration of FL118 enhancement of AMR-MeOAc to induce pancreatic cancer cell apoptosis and growth inhibition. [2020]

2. England pubmed.ncbi.nlm.nih.gov

A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Inhibition of KRAS, MEK and PI3K Demonstrate Synergistic Anti-Tumor Effects in Pancreatic Ductal Adenocarcinoma Cell Lines. [2022]

4. England pubmed.ncbi.nlm.nih.gov

KRAS-related proteins in pancreatic cancer. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Molecular targeting therapy for pancreatic cancer: current knowledge and perspectives from bench to bedside. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

K-RAS mutant pancreatic tumors show higher sensitivity to MEK than to PI3K inhibition in vivo. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Drugging RAS: Moving Beyond KRASG12C. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Dual Inhibition of KRASG12D and Pan-ERBB Is Synergistic in Pancreatic Ductal Adenocarcinoma. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy: SWOG S1115 Study Randomized Clinical Trial. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy of a Small-Molecule Inhibitor of KrasG12D in Immunocompetent Models of Pancreatic Cancer. [2023]