A Phase 2 Trial of MRTX849 Monotherapy and in Combination with Pembrolizumab in Patients with Advanced Non-Small Cell Lung Cancer with KRAS G12C Mutation

NOT ENROLLING
Protocol # :
21-244
Conditions
Advanced Non-Small Cell Lung Cancer
Metastatic Non-Small Cell Lung Cancer
Phase
II
Disease Sites
Lung
Principal Investigator
Janne, Pasi, A
Site Research Nurses
Callahan, Carragh
Hurley, Meaghan
Janell, Samantha
Kelley, Elaine
Lam, Ethan
Souza, Joseph
Sullivan, Molly, O'Brien

Trial Description

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 nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS >=50% and who are
candidates for first line treatment.

Eligibility Requirements

Inclusion Criteria:

- 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:

1. No evidence of brain metastases

2. Untreated brain metastases not needing immediate local therapy

3. Previously treated brain metastases not needing immediate local therapy

Exclusion Criteria:

- Phase 2 and Phase 3: Prior systemic treatment for locally advanced or metastatic NSCLC
including chemotherapy, immune checkpoint inhibitor therapy, or a therapy targeting
KRAS G12C mutation (e.g., AMG 510).

- Phase 2: Active brain metastases

- Phase 3: Patients with known central nervous system (CNS) lesions must not have any of
the following:

1. Any untreated brain lesions > 1.0 cm in size

2. Any brainstem lesions

3. Ongoing use of systemic corticosteroids for control of symptoms of brain lesions
at a total daily dose of > 10 mg of prednisone (or equivalent) prior to
randomization.

4. Have poorly controlled (> 1/week) generalized or complex partial seizures, or
manifest neurologic progression due to brain lesions notwithstanding CNS-directed
therapy

- Phase 3: Radiation to the lung > 30 Gy within 6 months prior to the first dose of
study treatment

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