Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03989115
Recruitment Status : Recruiting
First Posted : June 18, 2019
Last Update Posted : February 24, 2021
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Revolution Medicines, Inc.

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

Detailed Description:
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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 168 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
Estimated Primary Completion Date : March 31, 2022
Estimated Study Completion Date : April 30, 2022


Arm Intervention/treatment
Experimental: RMC-4630 and Cobimetinib
RMC-4630 and Cobimetinib for oral administration
Drug: RMC-4630
RMC-4630 for oral administration

Drug: Cobimetinib
Cobimetinib for oral administration
Other Name: GDC-0973, XL518

Experimental: RMC-4630 and Osimertinib
RMC-4630 and Osimertinib for oral administration
Drug: RMC-4630
RMC-4630 for oral administration

Drug: Drug: Osimertinib
Osimertinib for oral administration
Other Names:
  • Tagrisso
  • AZD9291




Primary Outcome Measures :
  1. 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

  2. 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 :
  1. Cmax [ Time Frame: up to 3 years ]
    Peak plasma concentration of RMC-4630 and cobimetinib or RMC-4360 and osimertinib

  2. Tmax [ Time Frame: up to 3 years ]
    Time to achieve peak plasma concentration of RMC-4630 and cobimetinib or RMC-4360 and osimertinib

  3. 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

  4. t1/2 [ Time Frame: up to 3 years ]
    Elimination half-life of RMC-4630 and cobimetinib or RMC-4360 and osimertinib

  5. 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

  6. 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

  7. 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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


Contacts
Layout table for location contacts
Contact: Revolution Medicines, Inc. (650) 779-2300 CT-Inquiries@RevMed.com

Locations
Show Show 25 study locations
Sponsors and Collaborators
Revolution Medicines, Inc.
Sanofi
Investigators
Layout table for investigator information
Study Director: Revolution Medicines, Inc. Revolution Medicines, Inc.
Layout table for additonal information
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: February 24, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Revolution Medicines, Inc.:
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:
Layout table for MeSH terms
Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action