Brief 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.
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.
Brief Title
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
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.
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.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
855-907-3286
Central Contact Email
Clinical.Trials@bms.com
Central Contact Role
Contact
Completion Date
Completion Date Type
Estimated
Conditions
Advanced Non-Small Cell Lung Cancer
Metastatic Non-Small Cell Lung Cancer
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 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
* 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
Inclusion 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 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
* 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
Gender
All
Gender Based
false
Keywords
KRAS G12C
Non-small cell lung cancer
NSCLC
Metastatic Non-Small Cell Lung Cancer
Adagrasib
Krazati
TPS
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04613596
Org Class
Industry
Org Full Name
Mirati Therapeutics Inc.
Org Study Id
CA239-0009
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
Objective Response Rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Outcome Measure
Phase 2: To evaluate the efficacy of Adagrasib monotherapy and in combination with pembrolizumab administered to patients having advanced/metastatic NSCLC.
Outcome Time Frame
22 months
Outcome Description
Progression Free Survival per RECIST 1.1 by Blinded Independent Central Review (BICR) and Overall Survival
Outcome Measure
Phase 3: To compare efficacy of Adagrasib in combination with pembrolizumab versus pembrolizumab
Outcome Time Frame
36 months
Secondary Ids
Secondary Id
CA239-0009
Secondary Id
849-007
Secondary Outcomes
Outcome Description
Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities.
Outcome Time Frame
22 months
Outcome Measure
Phase 2: To characterize the safety and tolerability of study treatments in selected populations
Outcome Description
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.
Outcome Time Frame
22 months
Outcome Measure
Phase 2: Duration of Response
Outcome Description
Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Outcome Time Frame
22 months
Outcome Measure
Phase 2: Progression Free Survival
Outcome Description
1-Year Survival rate
Outcome Time Frame
12 months
Outcome Measure
Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations
Outcome Description
Overall Survival (OS)
Outcome Time Frame
22 months
Outcome Measure
Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations
Outcome Description
Pharmacokinetics (PK) Blood plasma Adagrasib and potential metabolite concentrations
Outcome Time Frame
22 months
Outcome Measure
Phase 2: To evaluate the pharmacokinetics (PK) of study treatments by measuring blood plasma MRTX849 and potential metabolite concentrations.
Outcome Description
Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities.
Outcome Time Frame
36 months
Outcome Measure
Phase 3: To evaluate the safety and tolerability in the study population
Outcome Description
Pharmacokinetics (PK) Blood plasma Adagrasib and potential metabolite concentrations
Outcome Time Frame
36 months
Outcome Measure
Phase 3: To evaluate the PK of adagrasib administered in the study population
Outcome Description
Patient Reported Outcomes to measure quality of life
Outcome Time Frame
36 months
Outcome Measure
Phase 3: To evaluate health-related quality of life (HRQOL) and lung cancer specific symptoms in the study population
Outcome Description
Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Outcome Time Frame
36 months
Outcome Measure
Phase 3: Progression Free Survival per RECIST 1.1 by Investigator
Outcome Description
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.
Outcome Time Frame
36 months
Outcome Measure
Phase 3: Duration of Response (DOR) per RECIST 1.1 by Investigator and BICR
Outcome Description
Defined as the percent of patients documented to have a confirmed CR or PR.
Outcome Time Frame
36 months
Outcome Measure
Phase 3: Objective Response Rate (ORR) per RECIST 1.1 by Investigator and BICR
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
ADAGRASIB
PEMBROLIZUMAB