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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 : July 8, 2019
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).

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: RMC-4630 Drug: Cobimetinib 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
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 With Specific Genomic Aberrations
Actual Study Start Date : July 3, 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




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

  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


Secondary Outcome Measures :
  1. Cmax [ Time Frame: up to 3 years ]
    Peak plasma concentration of RMC-4630 and cobimetinib

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

  3. Area Under the Curve (AUC) [ Time Frame: up to 3 years ]
    Area under the plasma concentration time curve of RMC-4630 and cobimetinib

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

  5. 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

  6. Overall Response Rate (ORR) [ Time Frame: up to 3 years ]
    Overall response rate of RMC-4630 and cobimetinib per RECIST v1.1

  7. Duration of Response (DOR) [ Time Frame: up to 3 years ]
    Duration of response of RMC-4630 and cobimetinib 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
  • 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

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
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Contact: Revolution Medicines, Inc. (650) 779-2300 CT-Inquiries@RevolutionMedicines.com

Locations
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United States, Arizona
Honor Health Research Institute Not yet recruiting
Scottsdale, Arizona, United States, 85258
Contact: Study Coordinator         
Principal Investigator: Michael Gordon, MD         
United States, California
City of Hope Not yet recruiting
Duarte, California, United States, 91010
Contact: Study Coordinator         
Principal Investigator: Marianna Koczywas, MD         
UC Irvine - Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
Contact: Study Coordinator         
Principal Investigator: Sai-Hong Ignatius Ou, MD         
United States, Tennessee
Sarah Cannon Research Institute - Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact: Study Coordinator         
Principal Investigator: Johanna Bendell, MD         
Sponsors and Collaborators
Revolution Medicines, Inc.
Sanofi
Investigators
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Study Director: Revolution Medicines, Inc. Revolution Medicines, Inc.

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Responsible Party: Revolution Medicines, Inc.
ClinicalTrials.gov Identifier: NCT03989115     History of Changes
Other Study ID Numbers: RMC-4630-02
First Posted: June 18, 2019    Key Record Dates
Last Update Posted: July 8, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Revolution Medicines, Inc.:
advanced solid tumor
advanced solid malignancies
skin cancer
ovarian cancer
pancreatic cancer
endometrium/uterus cancer
bladder cancer
cervical cancer
neoplasm, squamous cell
esophageal neoplasms carcinoma, bronchogenic
bronchial neoplasms
lung neoplasms
respiratory tract neoplasms
thoracic neoplasms
neoplasms by site
neoplasms
SHP2
PTPN11
NSCLC
KRAS G12
BRAF Class 3
NF1 LOF
KRAS amplification
KRAS mutations
melanoma
carcinoma, non-small-cell lung
carcinoma, squamous cell
lung diseases
respiratory tract diseases