- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03989115
Dose-Esc/Exp RMC4630 & Cobi in Relapsed/Refractory Solid Tumors & RMC4630& Osi in EGFR+ Locally Adv/Meta NSCLC
May 31, 2023 updated by: Revolution Medicines, Inc.
Ph1b/2 Open-Label,Multicenter Dose-Esc & Dose-Exp Study of Combo RMC4630 & Cobimetinib in Participants w/Relapsed/Refractory Solid Tumors & Ph1b Study of RMC4630 w/Osimertinib in Participants w/EGFR Mutation+,Locally Adv or Meta NSCLC
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
113
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Seoul, Korea, Republic of, 110744
- Seoul National University Hospital
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Seoul, Korea, Republic of, 135-710
- Samsung Medical Center - PPDS
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Seoul Teugbyeolsi
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Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
- Severance Hospital Yonsei University Health System
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Arizona
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Scottsdale, Arizona, United States, 85258
- Honor Health Research Institute
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California
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Duarte, California, United States, 91010
- City of Hope
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Orange, California, United States, 92868
- UC Irvine - Chao Family Comprehensive Cancer Center
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Sacramento, California, United States, 95817
- UC Davis Comprehensive Cancer Center
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San Francisco, California, United States, 94115
- UC San Francisco - Helen Diller Family Comprehensive Cancer Center
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Colorado
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Aurora, Colorado, United States, 80045
- University of Colorado Cancer Center
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Florida
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Tampa, Florida, United States, 33612
- Moffitt Cancer Center
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Georgia
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Atlanta, Georgia, United States, 30322
- Winship Cancer Institute, Emory University
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Illinois
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Chicago, Illinois, United States, 60611
- Northwestern University
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute
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Michigan
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Detroit, Michigan, United States, 48201
- Karmanos Cancer Institute
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New York
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New York, New York, United States, 10021
- Memorial Sloan Kettering Cancer Center
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Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
- University of Oklahoma - Stephenson Cancer Center
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Oregon
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Portland, Oregon, United States, 97213
- Providence Cancer Institute, Franz Clinic
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
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Tennessee
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Nashville, Tennessee, United States, 37203
- Sarah Cannon Research Institute - Tennessee Oncology, PLLC
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Texas
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Austin, Texas, United States, 78712
- Dell Seton Medical Center at University of Texas
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Virginia
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Fairfax, Virginia, United States, 22031
- Virginia Cancer Specialists (Fairfax) - USOR
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Wisconsin
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Madison, Wisconsin, United States, 53792
- University of Wisconsin
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: RMC-4630 and Cobimetinib
RMC-4630 and Cobimetinib for oral administration
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RMC-4630 for oral administration
Cobimetinib for oral administration
Other Names:
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Experimental: RMC-4630 and Osimertinib
RMC-4630 and Osimertinib for oral administration
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RMC-4630 for oral administration
Osimertinib for oral administration
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events (AEs).
Time Frame: AEs were collected from the start of intervention through 30 days post last day of study drug taken. Participants were monitored/assessed for adverse events for a maximum of 17 months which includes a maximum duration of 16 months on treatment.
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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.
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AEs were collected from the start of intervention through 30 days post last day of study drug taken. Participants were monitored/assessed for adverse events for a maximum of 17 months which includes a maximum duration of 16 months on treatment.
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Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Cycle 1: Study Day 1 - Study Day 28 (28 days)
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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.
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Cycle 1: Study Day 1 - Study Day 28 (28 days)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cmax
Time Frame: 0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
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Peak plasma concentration of RMC-4630 and cobimetinib or RMC-4630 and osimertinib
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0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
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Tmax
Time Frame: 0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
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Time to achieve peak plasma concentration of RMC-4630 and cobimetinib or RMC-4630 and osimertinib
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0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
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Area Under the Curve (AUC)
Time Frame: 0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
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Area under the plasma concentration time curve of RMC-4630 and cobimetinib or RMC-4630 and osimertinib
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0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
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Accumulation Ratio
Time Frame: 0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
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AUC ratio (C1D15 versus C1D1) of RMC-4630 and cobimetinib or RMC-4630 and osimertinib
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0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
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Duration of Response (DOR)
Time Frame: Response assessment occurs from the start of intervention until the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first.
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Duration of response of RMC-4630 and cobimetinib or RMC-4630 and osimertinib per RECIST v1.1
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Response assessment occurs from the start of intervention until the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first.
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t1/2
Time Frame: 0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
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Elimination half-life of RMC-4630 and cobimetinib or RMC-4630 and osimertinib
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0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
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Overall Response Rate (ORR)
Time Frame: Response assessment occurs from the start of intervention until the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first.
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ORR is defined as the proportion of participants who achieve a CR or PR per RECIST v1.1.
ORR and the corresponding 95% two-sided confidence interval were derived.
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Response assessment occurs from the start of intervention until the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Revolution Medicines, Inc., Revolution Medicines, Inc.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 2, 2019
Primary Completion (Actual)
February 8, 2022
Study Completion (Actual)
February 8, 2022
Study Registration Dates
First Submitted
June 14, 2019
First Submitted That Met QC Criteria
June 14, 2019
First Posted (Actual)
June 18, 2019
Study Record Updates
Last Update Posted (Actual)
June 26, 2023
Last Update Submitted That Met QC Criteria
May 31, 2023
Last Verified
February 1, 2023
More Information
Terms related to this study
Keywords
- colorectal cancer
- NSCLC
- bladder cancer
- ovarian cancer
- pancreatic cancer
- SHP2
- KRAS amplification
- bronchial neoplasms
- lung neoplasms
- respiratory tract neoplasms
- neoplasms by site
- neoplasms
- lung diseases
- respiratory tract diseases
- advanced solid tumor
- gastrointestinal cancer
- KRAS mutations
- PTPN11
- cervical cancer
- skin cancer
- advanced solid malignancies
- endometrium/uterus cancer
- KRAS G12
- BRAF Class 3
- NF1 LOF
- carcinoma, non-small-cell lung
- neoplasm, squamous cell
- carcinoma, squamous cell
- esophageal neoplasms carcinoma, bronchogenic
- thoracic neoplasms
Additional Relevant MeSH Terms
Other Study ID Numbers
- RMC-4630-02
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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