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Clinical Trial 20577

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT03989115

Phase: Phase I/II
Prinicipal Investigator: Eric Haura

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Overview

Study 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

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); 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.

Objective

Primary Objectives: To characterize the safety and tolerability of the combination of RMC-4630 and cobimetinib in participants with relapsed/refractory solid tumors To define the MTD and RP2D and schedules for the combination of RMC-4630 and cobimetinib in participants with relapsed/refractory solid tumors Secondary Objectives: To characterize the plasma PK of RMC-4630 and cobimetinib when administered concurrently To estimate the anti-tumor effects of RMC-4630 in combination with cobimetinib at the RP2D in participants with relapsed/refractory solid tumors harboring specific genotypic aberrations in the RAS-MAPK pathway Tertiary/Exploratory Objectives: To estimate the anti-tumor effects of RMC-4630 in combination with cobimetinib in all participants To characterize the PD effects of RMC-4630 and cobimetinib in combination in blood and/or tumor tissue To identify PD markers of drug activity of RMC-4630 and cobimetinib in combination To evaluate preclinically predefined predictive genomic biomarker models and explore further predictive and prognostic biomarker strategies. Assessment of longitudinal effects of RMC-4630 and cobimetinib on the clonal dynamics of the tumor

Treatments

Therapies

Medications

AZD9291 (Osimertinib); Cobimetinib (); Osimertinib (); RMC-4630 ()

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

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