Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS G12C Mutation KRYSTAL-7
18 Years and older, Male and Female
CA239-0009 (primary)
NCI-2021-06578
849-007
CA239-0009
Summary
The Phase 2 portion of this study evaluates the efficacy and safety of MRTX849
monotherapy and in combination with pembrolizumab in cohorts of patients with advanced
NSCLC with KRAS G12C mutation and any PD-L1 TPS and who are candidates for first-line
treatment.
The Phase 3 portion of the study compares the efficacy of adagrasib in combination with
pembrolizumab versus pembrolizumab in patients with unresectable, locally advanced or
metastatic squamous or nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS >=50% and
who are candidates for first line treatment.
Objectives
The Phase 2 portion of this study will evaluate the efficacy and safety of MRTX849 as
monotherapy and in combination with pembrolizumab. There will be 3 cohorts of patients,
all of whom have KRAS G12C mutation, have advanced or metastatic NSCLC, and are
candidates for first-line treatment. 2 cohorts have PD-L1 TPS score <1% and are
randomized to MRTX849 monotherapy or MRTX849 in combination with pembrolizumab. The 3rd
cohort has PD-L1 TPS score of 1% or higher and is treated with MRTX849 and pembrolizumab
The Phase 3 portion of the study will randomize patients with squamous or nonsquamous
NSCLC with KRAS G12C mutation and TPS >=50% in the first-line setting to adagrasib plus
pembrolizumab or pembrolizumab. Primary efficacy objective is to compare efficacy between
experimental and comparator arms. Secondary and exploratory objectives include evaluation
of secondary efficacy endpoints, safety and tolerability, adagrasib PK, PROs, and
correlative genomic biomarkers for the combination regimen in the study population.
MRTX849 is an orally available small molecule inhibitor of KRAS G12C, and Pembrolizumab
(KEYTRUDA®) is a humanized monoclonal antibody that blocks the interaction between PD-1
and its ligands, PD-L1 and PD-L2.
Eligibility
- Phase 2: Histologically confirmed diagnosis of unresectable or metastatic NSCLC with KRAS G12C mutation and any PD-L1 TPS
- Phase 3: Histologically confirmed diagnosis of unresectable or metastatic squamous or nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS >=50%
- Phase 3: Presence of evaluable or measurable disease per RECIST
- Phase 3: CNS Inclusion - Based on screening brain imaging, patients must have one of the following:
- No evidence of brain metastases
- Untreated brain metastases not needing immediate local therapy
- Previously treated brain metastases not needing immediate local therapy
Treatment Sites in Georgia
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