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Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT03634982
Recruitment Status : Recruiting
First Posted : August 17, 2018
Last Update Posted : October 19, 2020
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Revolution Medicines, Inc.

Tracking Information
First Submitted Date  ICMJE August 10, 2018
First Posted Date  ICMJE August 17, 2018
Last Update Posted Date October 19, 2020
Actual Study Start Date  ICMJE September 28, 2018
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2018)
  • Number of participants with adverse events (AEs) [ Time Frame: up to 3 years ]
    Incidence, nature, and severity of treatment-emergent AEs and serious AEs, including incidence and severity of findings in laboratory values and vital signs for RMC-4630 monotherapy
  • Number of participants with dose limiting toxicities (DLTs) [ Time Frame: 28 days ]
    Incidence and nature of DLTs with RMC-4630 monotherapy
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2020)
  • Cmax [ Time Frame: up to 3 years ]
    Peak plasma concentration of RMC-4630
  • Tmax [ Time Frame: up to 3 years ]
    Time to achieve peak plasma concentration of RMC-4630
  • Area Under the Curve (AUC) [ Time Frame: up to 3 years ]
    Area under the plasma concentration time curve of RMC-4630
  • t1/2 [ Time Frame: up to 3 years ]
    Elimination half-life of RMC-4630
  • Accumulation Ratio [ Time Frame: up to 3 years ]
    Ratio of accumulation of RMC-4630 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 per RECIST v1.1
  • Duration of Response (DOR) [ Time Frame: up to 3 years ]
    Duration of response of RMC-4630 per RECIST v1.1
Original Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2018)
  • Cmax [ Time Frame: up to 3 years ]
    Peak plasma concentration of RMC-4630
  • Tmax [ Time Frame: up to 3 years ]
    Time to achieve peak plasma concentration of RMC-4630
  • Area Under the Curve (AUC) [ Time Frame: up to 3 years ]
    Area under the plasma concentration time curve of RMC-4630
  • t1/2 [ Time Frame: up to 3 years ]
    Elimination half-life of RMC-4630
  • Accumulation Ratio [ Time Frame: up to 3 years ]
    Ratio of accumulation of RMC-4630 from a single dose to steady state with repeated dosing
  • pERK [ Time Frame: up to 3 years ]
    On-treatment versus baseline comparison of pharmacodynamic markers of RMC-4630 (e.g., pERK [phosphorylated form of extracellular signal-regulated kinase]) on peripheral blood mononuclear cells or newly obtained tumor samples by immunoassays or immunohistochemistry (IHC)
  • Overall Response Rate (ORR) [ Time Frame: up to 3 years ]
    Overall response rate of RMC-4630 per RECIST v1.1
  • Duration of Response (DOR) [ Time Frame: up to 3 years ]
    Duration of response of RMC-4630 per RECIST v1.1
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors
Official Title  ICMJE A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of RMC-4630 Monotherapy in Adult Participants With Relapsed/Refractory Solid Tumors
Brief Summary The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).
Detailed Description This is an open-label, multicenter, Phase 1 study of oral RMC-4630 monotherapy in participants with advanced relapsed or refractory solid tumors. The study will include 2 components: 1) a Dose-Escalation Component for participants with relapsed or refractory solid tumors and 2) a Dose-Expansion Component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the RAS-MAPK pathway. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors
Intervention  ICMJE Drug: RMC-4630
RMC-4630 for oral administration
Study Arms  ICMJE Experimental: RMC-4630
RMC-4630 for oral administration
Intervention: Drug: RMC-4630
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: August 20, 2020)
210
Original Estimated Enrollment  ICMJE
 (submitted: August 14, 2018)
200
Estimated Study Completion Date  ICMJE October 1, 2021
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant (male or female) ≥18 years of age
  • Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Participants in the Dose-Expansion Component must have one of the following genotypic aberrations: KRAS amplifications, KRASG12C (NSCLC), BRAF Class 3, or NF1 LOF (NSCLC and gynecological cancers) mutations
  • Adequate hematologic, hepatic and renal function
  • Participant able to understand and voluntarily sign the informed consent form (ICF) and able to comply with the study visit schedule and other protocol requirements.
  • Participants willing to agree to not father a child/become pregnant and comply with effective contraception criteria

Exclusion Criteria:

  • Known or suspected leptomeningeal or brain metastases or spinal cord compression
  • Primary central nervous system (CNS) tumors
  • 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
  • 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@RevMed.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03634982
Other Study ID Numbers  ICMJE RMC-4630-01
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 August 2020

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