Clinical Trials /

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

NCT03634982

Description:

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).

Related Conditions:
  • Malignant Female Reproductive System Neoplasm
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: RMC-4630-01
  • NCT ID: NCT03634982

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
RMC-4630RMC-4630

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
RMC-4630ExperimentalRMC-4630 for oral administration
  • RMC-4630

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
      
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 serious AEs, including incidence and severity of findings in laboratory values and vital signs for RMC-4630 monotherapy

Secondary Outcome Measures

Measure:Cmax
Time Frame:up to 3 years
Safety Issue:
Description:Peak plasma concentration of RMC-4630
Measure:Tmax
Time Frame:up to 3 years
Safety Issue:
Description:Time to achieve peak plasma concentration of RMC-4630
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
Measure:t1/2
Time Frame:up to 3 years
Safety Issue:
Description:Elimination half-life of RMC-4630
Measure:Accumulation Ratio
Time Frame:up to 3 years
Safety Issue:
Description:Ratio of accumulation of RMC-4630 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 per RECIST v1.1
Measure:Duration of Response (DOR)
Time Frame:up to 3 years
Safety Issue:
Description:Duration of response of RMC-4630 per RECIST v1.1

Details

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

Trial Keywords

  • SHP2
  • PTPN11
  • NSCLC
  • EGFR
  • KRAS G12
  • BRAF Class 3
  • NF1 LOF
  • advanced solid tumor
  • advanced solid malignancies
  • melanoma
  • skin cancer
  • ovarian cancer
  • endometrium/uterus cancer
  • bladder cancer
  • cervical cancer
  • Carcinoma, Non-Small-Cell Lung
  • Neoplasms, 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
  • Neoplasms, Glandular and Epithelial
  • Gastrointestinal Neoplasms
  • Digestive System Neoplasms
  • Head and Neck Neoplasms
  • Digestive System Diseases
  • Esophageal Diseases
  • Gastrointestinal Diseases

Last Updated

October 19, 2020