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Phase 2 Trial of MRTX849 Monotherapy and in Combination With Pembrolizumab for NSCLC With KRAS G12C Mutation KRYSTAL-7

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ClinicalTrials.gov Identifier: NCT04613596
Recruitment Status : Recruiting
First Posted : November 3, 2020
Last Update Posted : November 24, 2021
Sponsor:
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Brief Summary:
This Phase 2 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.

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 Phase 2

Detailed Description:

This Phase 2 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 PDL-1 TPS score <1% and are randomized to MRTX849 monotherapy or MRTX849 in combination with pembrolizumab. The 3rd cohort has PDL-1 TPS score of 1% or higher and is treated with MRTX849 and pembrolizumab

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Sequential 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 in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation
Actual Study Start Date : December 2, 2020
Estimated Primary Completion Date : October 30, 2023
Estimated Study Completion Date : November 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1a: PD-L1 TPS <1%

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

o 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 once every 3 weeks (Cohort 1a).
Other Name: Adagrasib

Experimental: Cohort 1b: PD-L1 TPS <1%

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

o 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: Cohort 2: PD-L1 TPS ≥1%

PD-L1 TPS ≥1% - assign to:

o 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 once every 3 weeks (Cohort 2).

Other Name: Adagrasib




Primary Outcome Measures :
  1. Evaluate the efficacy of MRTX849 monotherapy in advanced/metastatic NSCLC with PDL1 <1%, and efficacy of MRTX849 in combination with pembrolizumab, based on the Objective Response Rate (ORR) using RECIST version 1.1 [ Time Frame: 22 months ]
    Objective Response Rate (ORR) RECIST 1.1


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

  2. Duration of Response (DOR) [ Time Frame: 22 months ]
    Evaluate efficacy of MRTX849 monotherapy and in combination with pembrolizumab in terms of duration of response

  3. Pharmacokinetics (PK) Blood plasma MRTX849 and potential metabolite concentrations [ Time Frame: 22 months ]
    To evaluate the pharmacokinetics (PK) of MRTX849 administered as monotherapy and in combination with pembrolizumab by measuring blood plasma MRTX849 and potential metabolite concentrations.



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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:

  • Histologically confirmed diagnosis of NSCLC (squamous or nonsquamous) with KRAS G12C mutation and known PD-L1 Tumor Proportion Score (TPS) score.
  • Unresectable or metastatic disease.

Exclusion Criteria:

  • 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).
  • Active brain metastases.

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@emergingmed.com

Locations
Show Show 52 study locations
Sponsors and Collaborators
Mirati Therapeutics Inc.
Investigators
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Study Director: Elise Horvath Walsh, MD Mirati Therapeutics Inc.
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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: November 24, 2021
Last Verified: November 2021
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
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
Adagrasib
Antineoplastic Agents, Immunological
Antineoplastic Agents