Clinical Trials /

Dose-Escalation/Expansion of RMC-4630 and Cobimetinib in Relapsed/Refractory Solid Tumors and RMC-4630 and Osimertinib in EGFR Positive Locally Advanced/Metastatic NSCLC

NCT03989115

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dose-Escalation/Expansion of RMC-4630 and Cobimetinib in Relapsed/Refractory Solid Tumors and RMC-4630 and Osimertinib in EGFR Positive Locally Advanced/Metastatic NSCLC
  • 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 and a Phase 1b Study of RMC-4630 With Osimertinib in Participants With EGFR Mutation Positive, Locally Advanced or Metastatic NSCLC

Clinical Trial IDs

  • ORG STUDY ID: RMC-4630-02
  • NCT ID: NCT03989115

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
RMC-4630RMC-4630 and Cobimetinib
CobimetinibGDC-0973, XL518RMC-4630 and Cobimetinib
Drug: OsimertinibTagrisso, AZD9291RMC-4630 and Osimertinib

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
RMC-4630 and CobimetinibExperimentalRMC-4630 and Cobimetinib for oral administration
  • RMC-4630
  • Cobimetinib
RMC-4630 and OsimertinibExperimentalRMC-4630 and Osimertinib for oral administration
  • RMC-4630
  • Drug: Osimertinib

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events (AEs)
Time Frame:up to 3 years
Safety Issue:
Description: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 or RMC-4360 and osimertinib

Secondary Outcome Measures

Measure:Cmax
Time Frame:up to 3 years
Safety Issue:
Description:Peak plasma concentration of RMC-4630 and cobimetinib or RMC-4360 and osimertinib
Measure:Tmax
Time Frame:up to 3 years
Safety Issue:
Description:Time to achieve peak plasma concentration of RMC-4630 and cobimetinib or RMC-4360 and osimertinib
Measure:Area Under the Curve (AUC)
Time Frame:up to 3 years
Safety Issue:
Description:Area under the plasma concentration time curve of RMC-4630 and cobimetinib or RMC-4360 and osimertinib
Measure:t1/2
Time Frame:up to 3 years
Safety Issue:
Description:Elimination half-life of RMC-4630 and cobimetinib or RMC-4360 and osimertinib
Measure:Accumulation Ratio
Time Frame:up to 3 years
Safety Issue:
Description:Ratio of accumulation of RMC-4630 and cobimetinib or RMC-4360 and osimertinib from a single dose to steady state with repeated dosing
Measure:Overall Response Rate (ORR)
Time Frame:up to 3 years
Safety Issue:
Description:Overall response rate of RMC-4630 and cobimetinib or RMC-4360 and osimertinib per RECIST v1.1
Measure:Duration of Response (DOR)
Time Frame:up to 3 years
Safety Issue:
Description:Duration of response of RMC-4630 and cobimetinib or RMC-4360 and osimertinib per RECIST v1.1

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Revolution Medicines, Inc.

Trial Keywords

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

Last Updated

October 29, 2020