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

a study on Lung Cancer Non-Small Cell Lung Cancer Lung Tumor

Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
completion around

Description

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.

Official Title

A Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

Details

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.

Keywords

Advanced Non-Small Cell Lung Cancer, Metastatic Non-Small Cell Lung Cancer, KRAS G12C, Non-small cell lung cancer, NSCLC, Adagrasib, Krazati, TPS, Lung Neoplasms, Non-Small-Cell Lung Carcinoma, Pembrolizumab

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

  • 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

Locations

  • San Francisco Veterans Affairs Medical Center accepting new patients
    San Francisco California 94121 United States
  • UCSF Helen Diller Family Comprehensive Cancer Center accepting new patients
    San Francisco California 94158 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Mirati Therapeutics Inc.
Links
BMS Clinical Trial Information BMS Clinical Trial Patient Recruiting
ID
NCT04613596
Phase
Phase 2/3 research study
Study Type
Interventional
Participants
Expecting 806 study participants
Last Updated
Contact us about this trial