Phase 2
N=113
Dose-Esc/Exp RMC4630 & Cobi in Relapsed/Refractory Solid Tumors & RMC4630& Osi in EGFR+ Locally Adv/Meta NSCLC
Solid Tumor
Bottom Line
View on ClinicalTrials.gov: NCT03989115 ↗Enrolled (actual)
113
Serious AEs
40.7%
Results posted
Jun 2023
Primary outcome: Primary: Number of Participants With Adverse Events (AEs). — 8; 6; 12; 7 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- RMC-4630 (Drug); Cobimetinib (Drug); Drug: Osimertinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Revolution Medicines, Inc.
- Primary completion
- Feb 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs). |
8; 6; 12; 7; 64; 7 | — |
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) |
1; 0; 3; 1; 0; 2 | — |
| SECONDARY Cmax |
214; 248; 469; 430; 354; 449 | — |
| SECONDARY Tmax |
2.94; 2.00; 1.99; 1.02; 2.00; 1.92 | — |
| SECONDARY Area Under the Curve (AUC) |
2570; 2580; 5510; 4610; 4700; 4720 | — |
| SECONDARY Accumulation Ratio |
1.36; 1.22; 1.24; 1.20; 1.19; 1.20 | — |
| SECONDARY Duration of Response (DOR) |
NA | — |
| SECONDARY t1/2 |
15.7; 16.1; 15.1; 16.2; 17.0; 16.9 | — |
| SECONDARY Overall Response Rate (ORR) |
0; 0; 0; 0; 1.82; 0 | — |
Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of RMC-4630 and cobimetinib in adult participants with relapsed/refractory solid tumors with specific genomic aberrations and to identify the recommended Phase 2 dose (RP2D); and to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of RMC-4630 and osimertinib in adult participants with EGFR mutation-positive locally advanced or metastatic NSCLC.
Eligibility Criteria
Inclusion Criteria
- Age ≥18 years
- For RMC-4630 + Cobimetinib only - Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anti-cancer treatments including approved drugs for oncogenic drivers in their tumor type.
- For RMC-4630 + Osimertinib only - Locally advanced or metastatic EGFR mutant NSCLC not amenable to curative surgery or radiotherapy
- For RMC-4630 + Cobimetinib only - Participants must have one of the following genotypic aberrations: KRAS mutations and amplifications, BRAF Class 3 mutations, or NF1 LOF mutations
- For RMC-4630 + Osimertinib only - Evidence of radiological documentation of progression with osimertinib monotherapy or an osimertinib containing regimen. Participants should not be considered a current candidate for 1st generation EGFR TKI's by the investigator.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
- Adequate hematological, hepatic, and renal function
- Capable of giving signed informed consent form (ICF). Willing and able to compile with study requirements and restrictions
- Life expectancy >12 weeks
- Female of childbearing potential and males with partners of childbearing potential must comply with effective contraception criteria .
Exclusion Criteria
- Primary central nervous system (CNS) tumors.
- Known or suspected leptomeningeal or brain metastases or spinal cord compression.
- For RMC-4630 + osimertinib arm only - Known or suspected Small cell, squamous, or pleomorphic lung transformations
- Clinically significant cardiac disease
- Active, clinically significant interstitial lung disease or pneumonitis
- History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO
- Known HIV infection or active/chronic hepatitis B or C infection.
- Any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy
- Females who are pregnant or breastfeeding
Data sourced from ClinicalTrials.gov (NCT03989115). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.