Dose-Escalation/Expansion of RMC-4630 and Cobimetinib in Relapsed/Refractory Solid Tumors and RMC-4630 and Osimertinib in EGFR Positive Locally Advanced/Metastatic NSCLC
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| ClinicalTrials.gov Identifier: NCT03989115 |
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Recruitment Status :
Completed
First Posted : June 18, 2019
Last Update Posted : September 1, 2022
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Sponsor:
Revolution Medicines, Inc.
Collaborator:
Sanofi
Information provided by (Responsible Party):
Revolution Medicines, Inc.
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Solid Tumor | Drug: RMC-4630 Drug: Cobimetinib Drug: Drug: Osimertinib | Phase 1 Phase 2 |
This open-label, phase 1b/2 dose-escalation and dose-expansion study is designed to evaluate the safety and maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of RMC-4630 in combination with cobimetinib in participants with relapsed/refractory solid tumors; and of RMC-4630 in combination with osimertinib in adult participants with EGFR mutation-positive locally advanced or metastatic NSCLC.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 113 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1b/2, Open-Label, Multicenter Dose-Escalation and Dose-Expansion Study of the Combination of RMC-4630 and Cobimetinib in Adult Participants With Relapsed/Refractory Solid Tumors and a Phase 1b Study of RMC-4630 With Osimertinib in Participants With EGFR Mutation Positive, Locally Advanced or Metastatic NSCLC |
| Actual Study Start Date : | July 2, 2019 |
| Actual Primary Completion Date : | February 8, 2022 |
| Actual Study Completion Date : | February 8, 2022 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: RMC-4630 and Cobimetinib
RMC-4630 and Cobimetinib for oral administration
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Drug: RMC-4630
RMC-4630 for oral administration Drug: Cobimetinib Cobimetinib for oral administration
Other Name: GDC-0973, XL518 |
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Experimental: RMC-4630 and Osimertinib
RMC-4630 and Osimertinib for oral administration
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Drug: RMC-4630
RMC-4630 for oral administration Drug: Drug: Osimertinib Osimertinib for oral administration
Other Names:
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Primary Outcome Measures :
- Number of participants with adverse events (AEs) [ Time Frame: up to 3 years ]Incidence, nature, and severity of treatment-emergent AEs and SAEs, graded according to the NCI CTCAE v5 for the combination of RMC-4360 and cobimetinib or RMC-4360 and osimertinib
- Number of participants with dose limiting toxicities (DLTs) [ Time Frame: 28 days ]Incidence and nature of DLTs for the combination of RMC-4630 and cobimetinib or RMC-4360 and osimertinib
Secondary Outcome Measures :
- Cmax [ Time Frame: up to 3 years ]Peak plasma concentration of RMC-4630 and cobimetinib or RMC-4360 and osimertinib
- Tmax [ Time Frame: up to 3 years ]Time to achieve peak plasma concentration of RMC-4630 and cobimetinib or RMC-4360 and osimertinib
- Area Under the Curve (AUC) [ Time Frame: up to 3 years ]Area under the plasma concentration time curve of RMC-4630 and cobimetinib or RMC-4360 and osimertinib
- t1/2 [ Time Frame: up to 3 years ]Elimination half-life of RMC-4630 and cobimetinib or RMC-4360 and osimertinib
- Accumulation Ratio [ Time Frame: up to 3 years ]Ratio of accumulation of RMC-4630 and cobimetinib or RMC-4360 and osimertinib from a single dose to steady state with repeated dosing
- Overall Response Rate (ORR) [ Time Frame: up to 3 years ]Overall response rate of RMC-4630 and cobimetinib or RMC-4360 and osimertinib per RECIST v1.1
- Duration of Response (DOR) [ Time Frame: up to 3 years ]Duration of response of RMC-4630 and cobimetinib or RMC-4360 and osimertinib per RECIST v1.1
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03989115
Locations
Show 24 study locations
Sponsors and Collaborators
Revolution Medicines, Inc.
Sanofi
Investigators
| Study Director: | Revolution Medicines, Inc. | Revolution Medicines, Inc. |
| Responsible Party: | Revolution Medicines, Inc. |
| ClinicalTrials.gov Identifier: | NCT03989115 |
| Other Study ID Numbers: |
RMC-4630-02 |
| First Posted: | June 18, 2019 Key Record Dates |
| Last Update Posted: | September 1, 2022 |
| Last Verified: | August 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Revolution Medicines, Inc.:
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SHP2 PTPN11 NSCLC KRAS G12 BRAF Class 3 NF1 LOF KRAS amplification KRAS mutations advanced solid tumor advanced solid malignancies bladder cancer carcinoma, non-small-cell lung neoplasm, squamous cell carcinoma, squamous cell esophageal neoplasms carcinoma, bronchogenic |
bronchial neoplasms lung neoplasms respiratory tract neoplasms thoracic neoplasms neoplasms by site neoplasms lung diseases respiratory tract diseases gastrointestinal cancer colorectal cancer skin cancer ovarian cancer pancreatic cancer endometrium/uterus cancer cervical cancer |
Additional relevant MeSH terms:
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Neoplasms Osimertinib Antineoplastic Agents |
Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |