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Dose-Escalation and Dose-Expansion of RMC-4630 and Cobimetinib in Relapsed/Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT03989115
Recruitment Status : Recruiting
First Posted : June 18, 2019
Last Update Posted : November 25, 2019
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Revolution Medicines, Inc.

Tracking Information
First Submitted Date  ICMJE June 14, 2019
First Posted Date  ICMJE June 18, 2019
Last Update Posted Date November 25, 2019
Actual Study Start Date  ICMJE July 3, 2019
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03989115 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • Cmax [ Time Frame: up to 3 years ]
    Peak plasma concentration of RMC-4630 and cobimetinib
  • Tmax [ Time Frame: up to 3 years ]
    Time to achieve peak plasma concentration of RMC-4630 and cobimetinib
  • Area Under the Curve (AUC) [ Time Frame: up to 3 years ]
    Area under the plasma concentration time curve of RMC-4630 and cobimetinib
  • t1/2 [ Time Frame: up to 3 years ]
    Elimination half-life of RMC-4630 and cobimetinib
  • Accumulation Ratio [ Time Frame: up yo 3 years ]
    Ratio of accumulation of RMC-4630 and cobimetinib 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 per RECIST v1.1
  • Duration of Response (DOR) [ Time Frame: up to 3 years ]
    Duration of response of RMC-4630 and cobimetinib per RECIST v1.1
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-Escalation and Dose-Expansion of RMC-4630 and Cobimetinib in Relapsed/Refractory Solid Tumors
Official Title  ICMJE 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 With Specific Genomic Aberrations
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).
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE
  • Drug: RMC-4630
    RMC-4630 for oral administration
  • Drug: Cobimetinib
    Cobimetinib for oral administration
    Other Name: GDC-0973, XL518
Study Arms  ICMJE Experimental: RMC-4630 and Cobimetinib
RMC-4630 and Cobimetinib for oral administration
Interventions:
  • Drug: RMC-4630
  • Drug: Cobimetinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 14, 2019)
144
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2022
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥18 years
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
  • Participants must have one of the following genotypic aberrations: KRAS mutations and amplifications, BRAF Class 3 mutations, or NF1 LOF mutations
  • 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.
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Revolution Medicines, Inc. (650) 779-2300 CT-Inquiries@RevolutionMedicines.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03989115
Other Study ID Numbers  ICMJE RMC-4630-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Revolution Medicines, Inc.
Study Sponsor  ICMJE Revolution Medicines, Inc.
Collaborators  ICMJE Sanofi
Investigators  ICMJE
Study Director: Revolution Medicines, Inc. Revolution Medicines, Inc.
PRS Account Revolution Medicines, Inc.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP