Recruiting NCT04613596

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

Phase II / Phase III Interventional Advanced Non-Small Cell Lung Cancer Metastatic Non-Small Cell Lung Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Adagrasib, Adagrasib, Adagrasib, Adagrasib.
Who it may be relevant to: Registry conditions: Advanced Non-Small Cell Lung Cancer, Metastatic Non-Small Cell Lung Cancer. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Austria, Belgium +42
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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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

Overview

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.

Detailed description

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.

Interventions

Drug Adagrasib
Adagrasib 400 mg twice daily (BID) in combination with pembrolizumab (Cohort 1a)
Drug Adagrasib
Adagrasib 600 mg BID monotherapy (Cohort 1b)
Drug Adagrasib
adagrasib 400 mg BID in combination with pembrolizumab
Drug Adagrasib
Adagrasib 400 mg BID + pembrolizumab 200 mg every Q3W
Drug Pembrolizumab
Pembrolizumab 200 mg IV Q3W

Primary outcome measures

Phase 2: To evaluate the efficacy of Adagrasib monotherapy and in combination with pembrolizumab administered to patients having advanced/metastatic NSCLC. [Time frame: 22 months]
Phase 3: To compare efficacy of Adagrasib in combination with pembrolizumab versus pembrolizumab [Time frame: 36 months]

Secondary outcome measures (11)

Phase 2: To characterize the safety and tolerability of study treatments in selected populations [Time frame: 22 months]
Phase 2: Duration of Response [Time frame: 22 months]
Phase 2: Progression Free Survival [Time frame: 22 months]
Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations [Time frame: 12 months]
Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations [Time frame: 22 months]
Phase 2: To evaluate the pharmacokinetics (PK) of study treatments by measuring blood plasma MRTX849 and potential metabolite concentrations. [Time frame: 22 months]
Phase 3: To evaluate the safety and tolerability in the study population [Time frame: 36 months]
Phase 3: To evaluate health-related quality of life (HRQOL) and lung cancer specific symptoms in the study population [Time frame: 36 months]
Phase 3: Progression Free Survival per RECIST 1.1 by Investigator [Time frame: 36 months]
Phase 3: Duration of Response (DOR) per RECIST 1.1 by Investigator and BICR [Time frame: 36 months]
Phase 3: Objective Response Rate (ORR) per RECIST 1.1 by Investigator and BICR [Time frame: 36 months]

Eligibility criteria

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 measurable disease per RECIST1.1
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

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:

Any untreated brain lesions > 2.0 cm in size
Any brainstem lesions
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.
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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Open label
Primary purpose: Treatment