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Also known as SAR442720
RMC-4630 · 2 trials · 2 indications
Evaluation of the antitumor effects of RMC-4630 and sotorasib in locally advanced or metastatic NSCLC patients with KRASG12C mutation with and without co-existing genetic aberrations in specific genes such as STK11/LKB1, KEAP1, and PIK3CA after failure of prior standard therapy. Objective Response Rate (%) is defined as the proportion of patients with Best Overall Response of confirmed CR, or PR. Response was confirmed by a repeat assessment no less than 28 days.
An adverse event (AE) was defined as any untoward medical occurrence in a participant, temporally associated with the use of a pharmaceutical / an investigational product, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product(s) was also an AE. All AEs and SAEs will be collected from the start of intervention until the safety visit or EOT visit, whichever is later. The number of safety-evaluable participants who experienced at least one treatment-emergent AE was reported per protocol.
Any toxicities occurring during the DLT observation period (cycle 1) that were considered R/T study treatment, including GR4 AEs; GR3 febrile neutropenia or hemorrhage; GR3 thrombocytopenia with clinically significant bleeding; GR ≥2 pneumonitis; GR3 hypertension or rash which does not improve or remains uncontrolled for \>5 or more days despite maximal supportive care; GR3 non hematologic AEs that remain uncontrolled for \>72 hours despite maximal supportive care; Concurrent elevation of AST or ALT \>3 × ULN \& total bilirubin \>2 × ULN or international normalized ratio (INR) \>1.5 in the absence of cholestasis and other causes; Grade 3 QTcF prolongation based on a triplicate ECG; Ejection fraction \<50% with an absolute decrease of \>10% from baseline; Retinal vein occlusion any grade; 50% or less dose intensity of RMC4630 and/or cobimetnib or osimertinib due to study drug related toxicity. Refer to protocol for further details.
| Arm | Type | Description |
|---|---|---|
| RMC-4630 and sotorasib, Safety Run-in | EXPERIMENTAL | Safety Run-In: RMC-4630 and sotorasib |
| RMC-4630 and sotorasib, Expansion | EXPERIMENTAL | Dose Expansion: RMC-4630 and sotorasib |
| RMC-4630 and Cobimetinib | EXPERIMENTAL | RMC-4630 and Cobimetinib for oral administration |
| RMC-4630 and Osimertinib | EXPERIMENTAL | RMC-4630 and Osimertinib for oral administration |
| Name | Type | Description |
|---|---|---|
| RMC-4630 | DRUG | RMC-4630 administered orally as a capsule |
| Sotorasib | DRUG | Sotorasib administered orally as a tablet |
| Cobimetinib | DRUG | Cobimetinib for oral administration |
| Drug: Osimertinib | DRUG | Osimertinib for oral administration |
Inclusion Criteria: * Subject must be ≥18 years of age. * Subject must have pathologically documented, locally advanced or metastatic KRASG12C NSCLC (not amenable to curative surgery) that has progressed on prior standard therapies (no more than 3 prior lines of therapies are allowed) Exclusion Cr...
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RMC-4630 is an investigational small molecule being studied in oncology for non-small cell lung cancer and solid tumors. It has been evaluated in combination regimens, including with sotorasib in KRAS G12C-mutant NSCLC after prior standard therapies, and with other targeted agents in relapsed or refractory solid tumors and EGFR-positive NSCLC.
RMC-4630 targets SHP2, a protein tyrosine phosphatase involved in signaling through the RAS/MAPK pathway. By inhibiting SHP2, the drug is designed to interfere with signaling that drives tumor growth, which is why it has been studied in combination with other targeted therapies in KRAS-mutant and EGFR-positive cancers.
RMC-4630 is being developed by Revolution Medicines, Inc., a clinical-stage oncology company that trades on the Nasdaq under the ticker RVMD. The company has advanced the SHP2 inhibitor through Phase 1 and Phase 2 clinical studies in solid tumors and non-small cell lung cancer.
RMC-4630 has reached Phase 2 clinical development. It is an investigational agent and has not been approved by the FDA. Its clinical program includes a completed Phase 2 combination study in KRAS G12C-mutant non-small cell lung cancer and a completed Phase 1 study in solid tumors and EGFR-positive NSCLC.
RMC-4630 has been studied in two completed trials. NCT05054725 was a Phase 2 study of RMC-4630 plus sotorasib in KRAS G12C-mutant non-small cell lung cancer after failure of prior standard therapies, enrolling 47 patients. NCT03989115 was a Phase 1 dose-escalation and expansion study in relapsed or refractory solid tumors and EGFR-positive NSCLC, enrolling 113 patients.
Yes. RMC-4630 studies have used biomarker selection, including enrollment of patients whose tumors carry KRAS G12C mutations or EGFR alterations. The Phase 2 trial NCT05054725 specifically enrolled non-small cell lung cancer patients with KRAS G12C mutations after prior standard therapies, reflecting a biomarker-defined population.