Phase Ib Trial of the KRAS G12C Inhibitor Adagrasib (MRTX849) in Combination With the PARP Inhibitor Olaparib in Patients With KRAS G12C Mutated Advanced Solid Tumors, With a Focus on Gynecological, Breast, Pancreatic and KEAP1 Mutated Non-small Cell Lung Cancers

Description

Primary Objectives

* To evaluate the safety and tolerability of adagrasib in combination with olaparib in participants with KRAS G12C mutant advanced solid tumors.
* To establish the maximum tolerated dose and/or recommended phase 2 dose (MTD/RP2D) of the combination in participants with KRAS G12C mutant advanced solid tumors.

Secondary Objectives

* To assess the preliminary antitumor activity of the combination of adagrasib in combination with olaparib using objective response rate (ORR) = RECISTv1.1 complete response plus partial response (CR+PR).

Exploratory Objectives

* To assess predictive biomarkers of response and resistance to the combination of adagrasib with olaparib.
* To evaluate the pharmacodynamic profile of the combination of adagrasib and olaparib in participants with KRAS G12C mutant advanced solid tumors.
* To assess potential mechanisms of response and resistance by comparing serially collected circulating tumor DNA (ctDNA) samples and biopsies in responders and non-responders.