Save

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

PHASE2PHASE3RECRUITING

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.

Simpliy with AI

Study 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.

Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

Simplify with AI

Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2020-12-02

Primary completion: 2028-10-31

Study completion finish: 2029-10-31

Study type

TREATMENT

Phase

PHASE2

PHASE3

Trial ID

NCT04613596

Intervention or treatment

DRUG: Adagrasib

DRUG: Pembrolizumab

Conditions

• Advanced Non-Small Cell Lung Cancer
• Metastatic Non-Small Cell Lung Cancer

Image related to Advanced Non-Small Cell Lung Cancer

Condition: Advanced Non-Small Cell Lung Cancer, Metastatic Non-Small Cell Lung Cancer
DRUG: Adagrasib and other drugs
Woolloongabba, Not Specified, Australia and more
Sponsor: Mirati Therapeutics Inc.

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Princess Alexandra Hospital

Research sites nearby

Select from list below to view details:

Princess Alexandra Hospital
Woolloongabba, Not Specified, Australia
Ballarat Regional Integrated Cancer Center
Ballarat, Not Specified, Australia
Flinders Medical Centre
Bedford Park, Not Specified, Australia
Local Institution - 007-004
Clayton, Not Specified, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase 2 Cohort 1a: PD-L1 TPS <1% Cohort 1a: Adagrasib twice daily (BID) in combination with pembrolizumab	DRUG: Adagrasib Adagrasib 400 mg twice daily (BID) in combination with pembrolizumab (Cohort 1a)
EXPERIMENTAL: Phase 2 Cohort 1b: PD-L1 TPS <1% Cohort 1b: Adagrasib BID monotherapy	DRUG: Adagrasib Adagrasib 600 mg BID monotherapy (Cohort 1b)
EXPERIMENTAL: Phase 2 Cohort 2: PD-L1 TPS ≥1% Cohort 2: Adagrasib BID in combination with pembrolizumab	DRUG: Adagrasib adagrasib 400 mg BID in combination with pembrolizumab
EXPERIMENTAL: Phase 3 Cohort 3 Investigational Arm Adagrasib BID in combination with pembrolizumab	DRUG: Adagrasib Adagrasib 400 mg BID + pembrolizumab 200 mg every Q3W
ACTIVE_COMPARATOR: Phase 3 Cohort 4 Comparator Arm Pembrolizumab	DRUG: Pembrolizumab Pembrolizumab 200 mg IV Q3W

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Phase 2: To evaluate the efficacy of Adagrasib monotherapy and in combination with pembrolizumab administered to patients having advanced/metastatic NSCLC.	Objective Response Rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)	22 months
Phase 3: To compare efficacy of Adagrasib in combination with pembrolizumab versus pembrolizumab	Progression Free Survival per RECIST 1.1 by Blinded Independent Central Review (BICR) and Overall Survival	36 months

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Phase 2: To characterize the safety and tolerability of study treatments in selected populations	Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities.	22 months
Phase 2: Duration of Response	Defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first.	22 months
Phase 2: Progression Free Survival	Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.	22 months
Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations	1-Year Survival rate	12 months
Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations	Overall Survival (OS)	22 months
Phase 2: To evaluate the pharmacokinetics (PK) of study treatments by measuring blood plasma MRTX849 and potential metabolite concentrations.	Pharmacokinetics (PK) Blood plasma Adagrasib and potential metabolite concentrations	22 months
Phase 3: To evaluate the safety and tolerability in the study population	Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities.	36 months
Phase 3: To evaluate the PK of adagrasib administered in the study population	Pharmacokinetics (PK) Blood plasma Adagrasib and potential metabolite concentrations	36 months
Phase 3: To evaluate health-related quality of life (HRQOL) and lung cancer specific symptoms in the study population	Patient Reported Outcomes to measure quality of life	36 months
Phase 3: Progression Free Survival per RECIST 1.1 by Investigator	Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.	36 months
Phase 3: Duration of Response (DOR) per RECIST 1.1 by Investigator and BICR	Defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first.	36 months
Phase 3: Objective Response Rate (ORR) per RECIST 1.1 by Investigator and BICR	Defined as the percent of patients documented to have a confirmed CR or PR.	36 months

Frequently Asked Questions

Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

No questions submitted. Be the first to ask a question!

You may be eligible to participate in this trial based on your search.Apply for study

Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

References

Clinical Trials Gov: 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