RMC-4630 for Cancer

Not currently recruiting at 11 trial locations

Overseen By Revolution Medicines, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Revolution Medicines, Inc.

Disqualifiers: Brain metastases, CNS tumors, Cardiac disease, Lung disease, Retinal conditions, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RMC-4630, an experimental drug for individuals with solid tumors that haven't responded to other treatments or who can't use standard treatments. The trial aims to determine the best dose of RMC-4630 for future studies and ensure its safety. This trial may suit individuals with solid tumors who haven't had success with other cancer drugs and have specific gene changes, such as KRAS or BRAF mutations. Participants must follow the study schedule and agree to use effective birth control. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

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

Is there any evidence suggesting that RMC-4630 is likely to be safe for humans?

Research has shown that RMC-4630 appears safe and manageable in early studies with patients who have certain types of cancer. In one study, patients taking RMC-4630 experienced no severe or life-threatening side effects related to the treatment. Most side effects were mild to moderate, such as fatigue and changes in blood test results, which are common in many cancer treatments.

Another study examined RMC-4630 combined with another drug. This combination was generally safe and did not cause severe side effects. These results suggest that RMC-4630 alone might also be safe.

Since this trial is in its early stages, the main goal is to understand how the body processes the drug and to determine the best dose. This phase helps ensure the treatment is safe enough before advancing to more extensive research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

RMC-4630 is unique because it targets a specific pathway involved in the growth of cancer cells, known as the SHP2 pathway. Most treatments for relapsed or refractory solid tumors focus on inhibiting tumor growth in a more general way, but RMC-4630 zeroes in on this specific mechanism, potentially offering a more targeted approach. Researchers are excited about this treatment because it could lead to fewer side effects and more effective management of tumors that have stopped responding to traditional therapies.

What evidence suggests that RMC-4630 might be an effective treatment for solid tumors?

Research has shown that RMC-4630, a SHP2 inhibitor, may help treat solid tumors. One study found that using RMC-4630 alone reduced the growth of a specific type of lung cancer by 71%. This suggests potential effectiveness, particularly for cancers with certain genetic changes. However, previous trials have indicated it might not work as well when used alone. The treatment could be more effective when combined with other therapies, though results when used alone remain promising for some cases. ^{1 4 5 6 7}

Who Is on the Research Team?

Revolution Medicines, Inc.

Principal Investigator

Revolution Medicines, Inc.

Are You a Good Fit for This Trial?

Inclusion Criteria

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Participants in the Dose-Expansion Component must have one of the following genotypic aberrations: KRAS amplifications, KRASG12C (NSCLC), BRAF Class 3, or NF1 LOF (NSCLC and gynecological cancers) mutations

Participant able to understand and voluntarily sign the informed consent form (ICF) and able to comply with the study visit schedule and other protocol requirements.

Exclusion Criteria

Known HIV infection

Females who are pregnant or breastfeeding

Known or suspected leptomeningeal or brain metastases or spinal cord compression

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Participants receive escalating doses of RMC-4630 to evaluate safety, tolerability, and pharmacokinetics

28 days

Dose-Expansion

Participants with specific mutations receive RMC-4630 to further evaluate safety and efficacy

up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RMC-4630

How Is the Trial Designed?

Group I: RMC-4630 Experimental Treatment 1 Intervention

RMC-4630 for oral administration

Who Is Running the Clinical Trial?

Revolution Medicines, Inc.

Lead Sponsor

Trials

14

Recruited

4,500+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Citations

1. revmed.com revmed.com/wp-content/uploads/2023/09/01LB001_Koczywas_RMC-4630-01.pdf

Anti-tumor Activity and Tolerability of the SHP2 Inhibitor ... Anti-tumor Activity and Tolerability of the SHP2 Inhibitor RMC-4630 as a Single Agent in Patients with. RAS-Addicted Solid Cancers.

2. onclive.com onclive.com/view/sotorasib-plus-shp2-inhibition-elicits-promising-preliminary-activity-in-kras-g12c-mutated-nsclc

Sotorasib Plus SHP2 Inhibition Elicits Promising ... The combination of sotorasib and the small molecule SHP2 inhibitor RMC-4630 led to an investigator-assessed objective response rate of 27% and ...

3. jto.org jto.org/article/S1556-0864(22)00363-X/fulltext

OA03.03 Sotorasib in Combination with RMC-4630, a ... The combination of sotorasib with RMC-4630 was safe and tolerable in patients with KRAS p.G12C-mutated solid tumors.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10401072/

SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted ... FIH trials of the first SHP2 inhibitors to enter the clinic (e.g., RMC-4630 and TNO155) clearly showed limited monotherapy activity and were not optimally ...

5. researchgate.net researchgate.net/publication/346440843_Intermittent_dosing_of_RMC-4630_a_potent_selective_inhibitor_of_SHP2_combined_with_the_MEK_inhibitor_cobimetinib_in_a_phase_1b2_clinical_trial_for_advanced_solid_tumors_with_activating_mutations_of_RA

Intermittent dosing of RMC-4630, a potent, selective ... RMC-4630 monotherapy has shown a 71% reduction in the growth of KRAS G12C NSCLC cells in an ongoing Phase 1 clinical trial (NCT03634982) [29] .

6. jto.org jto.org/article/S1556-0864(22)01135-2/fulltext

EP08.02-111 RMC-4630, a SHP2 Inhibitor, in Combination ... The present study is designed to evaluate the antitumor effects of RMC-4630 and sotorasib in KRASG12C NSCLC subjects with and without co-existing genetic ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03989115

Study Details | NCT03989115 | Dose-Esc/Exp RMC4630 & ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of RMC-4630 and cobimetinib in ...