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Clinical Trial 20577

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

Phase: Phase I/II
Principal Investigator: Haura, Eric

Call 813-745-6100
or 1-800-679-0775 Learn More

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

Therapy (NOS)

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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