RMC-9805 for Solid Cancers

Recruiting at 17 trial locations

Overseen By Revolution Medicines, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Revolution Medicines, Inc.

Must not be taking: KRAS inhibitors

Disqualifiers: CNS tumors, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 21 weeks

604 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, RMC-9805, for individuals with certain solid tumors that have a specific mutation called KRAS G12D. The goal is to determine the treatment's safety and tolerability, both alone and in combination with another drug, RMC-6236. Ideal candidates have advanced solid tumors with this mutation and have not responded to standard treatments or experienced adverse effects. Participants should not have brain tumors or difficulty swallowing medication. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive it.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatment RMC-9805 is promising in terms of safety for patients with certain solid tumors. In earlier studies, taking RMC-9805 orally led to early and significant drops in tumor markers. Importantly, it has a "manageable safety profile," meaning the side effects are generally tolerable.

Researchers are still studying the safety of RMC-9805 when used with another treatment, RMC-6236. Both treatments are in the early testing stages, focusing mainly on safety and tolerability for people.

Overall, while research is ongoing, the initial results are encouraging for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for solid cancers, like chemotherapy and radiation, target rapidly dividing cells but can affect healthy cells too, leading to significant side effects. RMC-9805 is unique because it specifically targets cancer cells by focusing on their particular vulnerabilities, which may reduce harm to normal cells. Researchers are excited about this treatment because it uses a new mechanism of action that might improve patient outcomes by being both more targeted and potentially more effective. Additionally, in combination with RMC-6236, it may enhance the treatment's effectiveness by attacking the cancer cells from multiple angles, offering hope for better control of the disease.

What evidence suggests that this trial's treatments could be effective for KRAS G12D-mutant solid tumors?

Research shows that RMC-9805, which participants in this trial may receive, may help treat certain types of solid tumors with a specific mutation called KRAS G12D. In earlier studies, about 30% of patients experienced tumor shrinkage with RMC-9805 alone, and 80% of patients maintained stable disease without progression. This trial will also explore combining RMC-9805 with another treatment, RMC-6236, which might enhance effectiveness, though the exact results remain under study. Early evidence suggests that RMC-9805 can lower cancer markers in the blood, indicating potential effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Revolution Medicines, Inc.

Principal Investigator

Revolution Medicines, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have a specific mutation called KRAS G12D. Participants must have tried standard treatments without success or could not tolerate them, and should be in fairly good health (ECOG status 0 or 1) with their organs working well. People can't join if they have issues absorbing pills, brain tumors, active brain metastases, spinal cord compression, or previous treatment with similar investigational drugs.

Inclusion Criteria

I am fully active or can carry out light work.

My cancer is advanced or has spread, and tests show a KRASG12D mutation.

My cancer has worsened or I couldn't tolerate the standard treatments.

Exclusion Criteria

I have or might have cancer spread to my brain, spinal cord, or its coverings.

I have been treated with drugs targeting the KRASG12D mutation or similar.

I have issues with my digestive system that might affect my ability to take pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RMC-9805 as monotherapy or in combination with RMC-6236, including dose exploration and dose expansion

21 weeks

Follow-up

Participants are monitored for safety, tolerability, and clinical activity after treatment

up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• RMC-9805

Trial Overview The study tests the safety and how well people can handle RMC-9805 in those who have certain types of cancer like lung, colorectal, pancreatic cancer etc., all of which share the KRAS G12D mutation. The main goal is to see what happens when patients take this new drug.

How Is the Trial Designed?

Group I: RMC-9805 plus RMC-6236 combination arm Experimental Treatment 2 Interventions

Dose exploration and dose expansion

Group II: RMC-9805 monotherapy arm Experimental Treatment 1 Intervention

Dose exploration and dose expansion

Who Is Running the Clinical Trial?

Revolution Medicines, Inc.

Lead Sponsor

Trials

14

Recruited

4,500+

Citations

1. ir.revmed.com ir.revmed.com/news-releases/news-release-details/revolution-medicines-presents-initial-data-zoldonrasib-rmc-9805

Revolution Medicines As of a December 2, 2024 data cutoff date, 90 solid tumor patients were treated with 1200 mg once daily (QD), the candidate recommended Phase 2 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06040541

Study of RMC-9805 in Participants With KRAS G12D- ... This study is to evaluate the safety and tolerability of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-mutant solid tumors.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.724

Preliminary safety, antitumor activity, and circulating tumor ... Oral RMC-9805 showed encouraging initial antitumor activity with early and deep reductions in KRAS G12D ctDNA in patients with KRAS G12D PDAC.

4. onclive.com onclive.com/view/rmc-9805-triggers-tumor-regressions-in-kras-g12d-mutant-pancreatic-cancer

RMC-9805 Triggers Tumor Regressions in KRAS G12D ... RMC-9805 demonstrated a 30% objective response rate and 80% disease control rate in KRAS G12D–mutant PDAC patients. The phase 1/1b study ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12302276/

Drugging the 'undruggable' KRAS: breakthroughs, challenges ... RMC-9805 is currently being evaluated in a phase I trial for patients with advanced KRASG12D-mutant solid tumors (NCT06040541). Figure 3. Figure 3 · Open in a ...

6. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT019/762489/Abstract-CT019-Preliminary-safety-and-antitumor

Preliminary safety and antitumor activity of zoldonrasib (RMC ... Results: As of a December 2, 2024 data cutoff, 211 patients with KRAS G12D solid tumors received 5 escalating dose levels of zoldonrasib ...

7. onclive.com onclive.com/view/preliminary-safety-and-antitumor-activity-of-zoldonrasib-rmc-9805-an-oral-ras-on-g12d-selective-tri-complex-inhibitor-in-patients-with-kras-g12d-nonsmall-cell-lung-cancer-nsclc-from-a-phase-1-study-in-advanced-solid-tumors

Preliminary Safety and Antitumor Activity of Zoldonrasib ... Zoldonrasib, a selective RAS(ON) G12D inhibitor, demonstrates encouraging antitumor activity and a manageable safety profile in patients with previously ...