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

Purpose

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.

Conditions

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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: 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 > 2.0 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

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
MRTX849 Monotherapy, MRTX849 in Combination with Pembrolizumab and Pembrolizumab alone
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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)
    Other names:
    • Pembrolizumab
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
    Other names:
    • 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
    Other names:
    • Pemrolizumab
Active Comparator
Phase 3 Cohort 4 Comparator Arm 		Pembrolizumab
  • Drug: Pembrolizumab
    Pembrolizumab 200 mg IV Q3W

Recruiting Locations

USOR - Arizona Oncology - Prescott Valley
Prescott Valley, Arizona 86301
Contact:
Allan Espinosa Morazan, Site 007-556
928-775-9430

Arizona Clinical Research Center
Tucson, Arizona 85715
Contact:
Manuel Modiano, Site 007-568
520-290-2510

Highlands Oncology Group - Springdale
Springdale, Arkansas 72762
Contact:
Eric Schaefer, Site 007-978
479-872-8130

Providence - Saint Joseph Home Health - Anaheim
Anaheim, California 92805
Contact:
Giribala Patel, Site 007-899
714-446-5900

The Oncology Institute of Hope and Innovation - Corporate Office
Cerritos, California 90703
Contact:
Omkar Marathe, Site 007-898
562-693-4477

MemorialCare - Long Beach Medical Center
Long Beach, California 90806
Contact:
Nilesh Vora, Site 007-936
562-997-4070

TRIO - Cancer & Blood Specialty Clinic - Los Alamitos
Los Alamitos, California 90720
Contact:
Nihal Abdulla, Site 007-779
562-706-6648

San Francisco Veterans Affairs Medical Center
San Francisco, California 94121
Contact:
Sunny Wang, Site 007-581
415-221-4810x23380

UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California 94158
Contact:
Collin Blakely, Site 007-540
415-502-6959

Providence Medical Group - Santa Rosa
Santa Rosa, California 95403
Contact:
Manasa Vulchi, Site 007-858
707-521-3830

Stockton Hematology Oncology Medical Group (SHOMG) - Stockton (Suite B)
Stockton, California 95219
Contact:
Sunny K. Philip, Jr., Site 007-582
209-466-2626

USOR - Rocky Mountain Cancer Centers - Lone Tree
Lone Tree, Colorado 80124
Contact:
Robert Jotte, Site 007-872
303-430-2700

Eastern Connecticut Hematology and Oncology Associates
Norwich, Connecticut 06360
Contact:
Dennis Slater, Site 007-949
860-886-8362

GenesisCare USA
Aventura, Florida 33180
Contact:
Edgardo Santos, Site 007-552
239-938-9315

Bay Pines Veterans Affairs Healthcare System
Bay Pines, Florida 33744
Contact:
Ryan Burri, Site 007-593
727-398-6661

SCRI - Florida Cancer Specialists - South Region Research Office
Fort Myers, Florida 33901
Contact:
Fadi Kayali, Site 007-922
239-274-9930

21st Century Oncology of Jacksonville - North Lee Street
Jacksonville, Florida 32204
Contact:
Troy Guthrie, Site 007-853
904-805-7061

Cancer Specialists of North Florida - Southpoint
Jacksonville, Florida 32256
Contact:
Gaurav Trikha, Site 007-562
203-530-1728

Miami Veterans Affairs Healthcare System
Miami, Florida 33125-1624
Contact:
Gregory Holt, Site 007-594
305-575-7000

AdventHealth Orlando
Orlando, Florida 32803
Contact:
Mark Socinski, Site 007-896
412-647-2811

USOR - Woodlands Medical Specialists
Pensacola, Florida 32503
Contact:
Michael Poiesz, Site 007-877
850-696-4000

SCRI - Florida Cancer Specialists - Tallahassee Cancer Center
Tallahassee, Florida 32308
Contact:
Augusto Villegas, Site 007-924
904-613-4275

James A. Haley Veterans Hospital
Tampa, Florida 33612
Contact:
John Accomando, Site 007-937
813-391-7763

SCRI - Florida Cancer Specialists - West Palm Beach
West Palm Beach, Florida 33401
Contact:
Barry Berman, Site 007-926
407-933-2775

University Cancer & Blood Center (UCBC) - Athens
Athens, Georgia 30607
Contact:
Gustavo Westin, Site 007-941
706-353-2990

Central Georgia Cancer Care - Macon
Macon, Georgia 31201
Contact:
Bradley Sumrall, Site 007-5478
4787417145

Northwest Georgia Oncology Centers Wellstar - Marietta
Marietta, Georgia 30060
Contact:
Steven McCune, Site 007-786
770-281-5162

University of Chicago
Chicago, Illinois 60637
Contact:
Marina Garassino, Site 007-972
718-675-2060

Loyola University Medical Center
Maywood, Illinois 60153
Contact:
Nan Sethakorn, Site 007-064

USOR - Illinois Cancer Specialists - Niles
Niles, Illinois 60714
Contact:
David Hakimian, Site 007-883
847-827-9060

Advocate Medical Group Oncology
Park Ridge, Illinois 60068
Contact:
Jason Macklis, Site 007-567
000-000-0000

Goshen Center for Cancer Care
Goshen, Indiana 46526
Contact:
Ebenezer Kio, Site 007-943
574-364-2848

MidAmerica Cancer Care - Research
Merriam, Kansas 66204
Contact:
Jaswinder Singh, Site 007-5484
8162764700

Cancer Center of Kansas - Wichita - Heritage Plaza
Wichita, Kansas 67214
Contact:
Shaker Dakhil, Site 007-942
316-262-4467

Lexington Medical Cancer Center Hematology/Oncology
Lexington, Kentucky 40503
Contact:
Firas Badin, Site 007-965
859-260-6100

University of Louisville
Louisville, Kentucky 40202
Contact:
Goetz Kloecker, Site 007-388

Pontchartrain Cancer Center - Covington Office
Covington, Louisiana 70433
Contact:
David Oubre, Site 007-994
985-875-1202

The Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland 21231
Contact:
Kristen Marrone, Site 007-944
410-550-1711

Dana-Farber Cancer Institute
Boston, Massachusetts 02215
Contact:
Pasi Janne, Site 007-808
617-632-6036

Dana-Farber Cancer Institute at St. Elizabeths Medical Center
Brighton, Massachusetts 02135
Contact:
Alys Malcolm, Site 007-5483

Brigham and Womens/Mass General Health Care Center at Foxborough
Foxborough, Massachusetts 02035
Contact:
Naeem Tahir, Site 007-5480
7344536970

Dana-Farber Cancer Institute - Merrimack Valley
Methuen, Massachusetts 01844
Contact:
Pedro Sanz-Altamira, Site 007-5482
9786202020

Dana-Farber Brigham and Womens Cancer Center at Milford Regional
Milford, Massachusetts 01757
Contact:
Alexandra Bailey, Site 007-5479
7813379091

Dana-Farber Brigham Cancer Center at South Shore Health
South Weymouth, Massachusetts 02190
Contact:
Randi Carhart, Site 007-5481
7816244800

USOR - Minnesota Oncology - Burnsville
Burnsville, Minnesota 55337
Contact:
Sandeep Jain, Site 007-589

Jackson Oncology Associates - The Hederman Cancer Center
Jackson, Mississippi 39202
Contact:
Natale Sheehan, Site 007-588
601-355-2485

Nebraska Cancer Specialists - Midwest Cancer Center - Legacy
Omaha, Nebraska 68130
Contact:
Mary Wells, Site 007-590
531-329-3667

OptumCare Nevada
Las Vegas, Nevada 89106
Contact:
Russell Gollard, Site 007-938
000-000-0000

Astera Cancer Care - East Brunswick
East Brunswick, New Jersey 08816
Contact:
Bruno Fang, Site 007-975
301-435-5332

John Theurer Cancer Center
Hackensack, New Jersey 07601
Contact:
Martin Gutierrez, Site 007-854
954-267-7700

Holy Name Medical Center
Teaneck, New Jersey 07666
Contact:
Yadyra Rivera, Site 007-784
201-227-6008

New York Oncology Hematology - Albany Medical Center
Albany, New York 12208
Contact:
Makenzi Evangelist, Site 007-861
518-489-2607

Montefiore Medical Center
The Bronx, New York 10467
Contact:
Balazs Halmos, Site 007-945
718-405-8404

Duke University Medical Center
Durham, North Carolina 27710
Contact:
Thomas Stinchcombe, Site 007-946
919-613-2000

USOR - Oncology Hematology Care - Blue Ash
Cincinnati, Ohio 45242
Contact:
Patrick Ward, Site 007-893
513-751-2273

University Hospitals Cleveland Medical Center
Cleveland, Ohio 44106
Contact:
Melinda Hsu, Site 007-849
216-286-6505

Mark H. Zangmeister Cancer Center
Columbus, Ohio 43219
Contact:
Jorge Rios-perez, Site 007-930
502-561-7301

Kettering Health Cancer Center - Main Campus
Kettering, Ohio 45429
Contact:
Alejandro Calvo, Site 007-836
855-500-2873

Tricounty Hematology and Oncology - Massillon
Massillon, Ohio 44646
Contact:
Noman Rafique, Site 007-5486
3302686167

USOR - Willamette Valley Cancer Institute and Research Center - Eugene
Eugene, Oregon 97401
Contact:
Bo Wang, Site 007-889
541-683-5001

Oregon Oncology Specialists
Salem, Oregon 97301
Contact:
Janelle Meyer, Site 007-967
708-327-3180

Veterans Affairs Pittsburgh Healthcare System - University Drive Campus
Pittsburgh, Pennsylvania 15240
Contact:
James Herman, Site 007-5477
4126237769

Avera Cancer Institute
Sioux Falls, South Dakota 57105
Contact:
Benjamin Solomon, Site 007-940
605-322-6900

West Cancer Center & Research Institute - East Campus
Germantown, Tennessee 38138
Contact:
Ramakrishna Battini, Site 007-916
901-683-0055

Tennessee Oncology - Nashville - Centennial Clinic - Medical Oncology
Nashville, Tennessee 37203
Contact:
Melissa Johnson, Site 007-928
615-329-7274

USOR - Texas Oncology - Dallas Fort Worth (DFW) - South Austin
Austin, Texas 78745
Contact:
James Uyeki, Site 007-892
512-427-9400

Texas Oncology - Dallas Fort Worth (DFW) - Baylor Charles A. Sammons Cancer Center
Dallas, Texas 75246
Contact:
Kartik Konduri, Site 007-879
214-370-1000

USOR - Texas Oncology Northeast Texas - Denison
Denison, Texas 75020
Contact:
Amir Faridi, Site 007-890
000-000-0000

USOR - Texas Oncology - San Antonio Medical Center
Fredericksburg, Texas 78624
Contact:
Angel Mier-Hicks, Site 007-927
210-595-5300

USOR - Texas Oncology - Dallas Fort Worth (DFW) - Odessa West Texas Cancer Center
Odessa, Texas 79761
Contact:
Pankaj Khandelwal, Site 007-554
000-000-0000

USOR - Texas Oncology - The Woodlands
The Woodlands, Texas 77380
Contact:
Kruti Sheth Nair, Site 007-894
281-298-8907

USOR - Virginia Cancer Specialists - Fairfax Office
Fairfax, Virginia 22031
Contact:
Alexander Spira, Site 007-814
703-280-5390

Virginia Cancer Institute - West End
Richmond, Virginia 23229
Contact:
Thomas Weart, Site 007-539
804-287-3000

USOR - Northwest Cancer Specialists, P.C. dba Compass Oncology - Vancouver Cancer Center
Vancouver, Washington 98684
Contact:
Anthony Van Ho, Site 007-885
503-885-5411

More Details

Status
Recruiting
Sponsor
Mirati Therapeutics Inc.

Study Contact

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
855-907-3286
Clinical.Trials@bms.com

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.