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

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

Tracking Information

• First Submitted Date: August 10, 2018
• First Posted Date: August 17, 2018
• Last Update Posted Date: October 19, 2020
• Actual Study Start Date: September 28, 2018
• Estimated Primary Completion Date: October 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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 (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: Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors
• Official Title: 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumors

Intervention

Drug: RMC-4630

RMC-4630 for oral administration

Study Arms

Experimental: RMC-4630

RMC-4630 for oral administration

Intervention: Drug: RMC-4630

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 20, 2020): 210
• Original Estimated Enrollment (submitted: August 14, 2018): 200
• Estimated Study Completion Date: October 1, 2021
• Estimated Primary Completion Date: October 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03634982
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: Revolution Medicines, Inc.
• Study Sponsor: Revolution Medicines, Inc.
• Collaborators: Sanofi

Investigators

• Study Director: Revolution Medicines, Inc.; Revolution Medicines, Inc.

• PRS Account: Revolution Medicines, Inc.
• Verification Date: August 2020