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Trial record 1 of 1 for:    849-007
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Phase 2 Trial of MRTX849 Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients KRAS G12C Mutation KRYSTAL-7

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04613596
Recruitment Status : Recruiting
First Posted : November 3, 2020
Last Update Posted : June 9, 2023
Sponsor:
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Study Description
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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 plus chemotherapy 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.


Condition or disease Intervention/treatment Phase
Advanced Non-Small Cell Lung Cancer Metastatic Non-Small Cell Lung Cancer Drug: MRTX849 Monotherapy Drug: MRTX849 in Combination with Pembrolizumab Drug: Phase 3 comparator arm Phase 2 Phase 3

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

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 nonsquamous NSCLC with KRAS G12C mutation and TPS <50% in the first-line setting to adagrasib plus pembrolizumab or pembrolizumab plus chemotherapy. Primary efficacy endpoints are PFS and OS. 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 950 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: MRTX849 Monotherapy and in Combination with Pembrolizumab
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Trial of MRTX849 Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination With Pembrolizumab Versus Pembrolizumab Plus Chemotherapy in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation
Actual Study Start Date : December 2, 2020
Estimated Primary Completion Date : March 31, 2028
Estimated Study Completion Date : March 31, 2029

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase 2 Cohort 1a: PD-L1 TPS <1%

PD-L1 TPS <1% - randomize 1:1:

Cohort 1a: MRTX849 twice daily (BID) in combination with pembrolizumab

 Drug: MRTX849 in Combination with Pembrolizumab
MRTX849 Inhibitor will be administered orally twice daily in a continuous regimen. Pembrolizumab is administered as an intravenous infusion at a 200 mg dose once every 3 weeks then after 9 months patients may switch to a 400 mg dose administered every 6 weeks. Pembrolizumab treatment may continue up to 24 months (Cohort 3).
Other Name: Adagrasib
Experimental: Phase 2 Cohort 1b: PD-L1 TPS <1%

PD-L1 TPS <1% - randomize 1:1:

Cohort 1b: MRTX849 BID monotherapy

 Drug: MRTX849 Monotherapy
MRTX849 Inhibitor will be administered orally twice daily in a continuous regimen (Cohort 1b).
Other Name: Adagrasib
Experimental: Phase 2 Cohort 2: PD-L1 TPS ≥1%

PD-L1 TPS ≥1% - assign to:

Cohort 2: MRTX849 BID in combination with pembrolizumab

 Drug: MRTX849 in Combination with Pembrolizumab

MRTX849 Inhibitor will be administered orally twice daily in a continuous regimen.

Pembrolizumab is administered as an intravenous infusion at a 200 mg dose once every 3 weeks then after 9 months patients may switch to a 400 mg dose administered every 6 weeks. Pembrolizumab treatment may continue up to 24 months (Cohort 2).

Other Name: Adagrasib
Experimental: Phase 3 Cohort 3: PD-L1 TPS<50% randomized 1:1 with comparator arm
Cohort 3: Adagrasib BID in combination with pembrolizumab
 Drug: MRTX849 in Combination with Pembrolizumab

MRTX849 Inhibitor will be administered orally twice daily in a continuous regimen.

Pembrolizumab is administered as an intravenous infusion at a 200 mg dose once every 3 weeks then after 9 months patients may switch to a 400 mg dose administered every 6 weeks. Pembrolizumab treatment may continue up to 24 months (Cohort 2).

Other Name: Adagrasib
Active Comparator: Phase 3 Cohort 4: PD-L1 TPS <50% randomized 1:1 with experimental arm
Cohort 4: Pembrolizumab in combination with platinum agent and pemetrexed
 Drug: Phase 3 comparator arm
Pembrolizumab + platinum (cisplatin 75 mg/m2 OR carboplatin area under the curve (AUC) 5 mg/mL/min on Day 1 every 3 weeks for 4-6 cycles) + pemetrexed 500 mg/m2 (with vitamin supplementation) every 3 weeks for 4-6 cycles, followed by pembrolizumab 200 mg plus pemetrexed 500 mg/m2 every 3 weeks until progression. After 9 months, patients may switch to a pembrolizumab 400 mg dose administered every 6 weeks.
Other Name: Pembrolizumab, platinum, pemetrexed


Outcome Measures
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Primary Outcome Measures :
  1. Phase 2: To evaluate the efficacy of MRTX849 monotherapy and in combination with pembrolizumab administered to patients having advanced/metastatic NSCLC. [ Time Frame: 22 months ]
    Objective Response Rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

  2. Phase 3: To compare efficacy of adagrasib in combination with pembrolizumab versus pembrolizumab plus chemotherapy [ Time Frame: 62 months ]
    Overall Survival and Progression Free Survival


Secondary Outcome Measures :
  1. Phase 2: To characterize the safety and tolerability of study treatments in selected populations [ Time Frame: 22 months ]
    Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities.

  2. Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations [ Time Frame: 22 months ]
    Duration of Response (DOR), Progression - Free Survival (PFS), 1-Year Survival rate, Overall Survival (OS)

  3. Phase 2: To evaluate the pharmacokinetics (PK) of study treatments by measuring blood plasma MRTX849 and potential metabolite concentrations. [ Time Frame: 22 months ]
    Pharmacokinetics (PK) Blood plasma MRTX849 and potential metabolite concentrations

  4. Phase 3: To evaluate the safety and tolerability in the study population [ Time Frame: 62 months ]
    Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities.

  5. Phase 3: To evaluate the PK of adagrasib administered in the study population [ Time Frame: 62 months ]
    Pharmacokinetics (PK) Blood plasma MRTX849 and potential metabolite concentrations

  6. Phase 3: To evaluate health-related quality of life (HRQOL) and lung cancer specific symptoms in the study population [ Time Frame: 62 months ]
    Patient Reported Outcomes to measure quality of life

  7. Phase 3: To evaluate secondary efficacy endpoints in the study population [ Time Frame: 62 months ]
    PFS, ORR, and DOR


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04613596


Contacts
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Contact: Mirati Therapeutics Study Locator Services 18448935530 miratistudylocator@careboxhealth.com

Locations
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Sponsors and Collaborators
Mirati Therapeutics Inc.
Investigators
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Study Director: Viola Chen, MD Mirati Therapeutics Inc.
More Information
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Responsible Party: Mirati Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04613596    
Other Study ID Numbers: 849-007
First Posted: November 3, 2020    Key Record Dates
Last Update Posted: June 9, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mirati Therapeutics Inc.:
KRAS G12C
Non-small cell lung cancer
NSCLC
Metastatic Non-Small Cell Lung Cancer
 Adagrasib
Krazati
TPS
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
 Pembrolizumab
Pemetrexed
Adagrasib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors