Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1

A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Cancer; Advanced Cancer; Malignant Neoplastic Disease
• Intervention / Treatment: Drug: MRTX849; Drug: Pembrolizumab; Drug: Cetuximab; Drug: Afatinib

Detailed Description

This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.

• Study Type: Interventional
• Enrollment (Actual): 731
• Phase: Phase 2; Phase 1

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Puerto Rico
  • PR
    • San Juan, PR, Puerto Rico, 00935
      • Local Institution - 001-900
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Local Institution - 001-826
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Local Institution - 001-965
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Local Institution - 001-821
    • Tucson, Arizona, United States, 85704
      • Local Institution - 001-873-A
    • Tucson, Arizona, United States, 85704
      • Local Institution - 001-873
  • California
    • Bellflower, California, United States, 90706
      • Local Institution - 001-840-B
    • Beverly Hills, California, United States, 90211
      • Local Institution - 001-834
    • Duarte, California, United States, 91010
      • Local Institution - 001-843
    • Dublin, California, United States, 94568
      • Local Institution - 001-850-K
    • Fullerton, California, United States, 92835
      • Local Institution - 001-851
    • Harbor City, California, United States, 90710
      • Local Institution - 001-840-C
    • La Jolla, California, United States, 92093
      • Local Institution - 001-805
    • Los Alamitos, California, United States, 90720
      • Local Institution - 001-779
    • Los Angeles, California, United States, 90027
      • Local Institution - 001-840
    • Los Angeles, California, United States, 90067
      • Local Institution - 001-578
    • Newport Beach, California, United States, 92663
      • Local Institution - 001-847
    • Oakland, California, United States, 94611
      • Local Institution - 001-850-B
    • Orange, California, United States, 92868
      • Local Institution - 001-803
    • Roseville, California, United States, 95661
      • Local Institution - 001-850-C
    • Sacramento, California, United States, 95814
      • Local Institution - 001-850-J
    • Sacramento, California, United States, 95825
      • Local Institution - 001-850-D
    • San Diego, California, United States, 92111
      • Local Institution - 001-845
    • San Diego, California, United States, 92120
      • Local Institution - 001-840-A
    • San Francisco, California, United States, 94080
      • Local Institution - 001-850-H
    • San Francisco, California, United States, 94115
      • Local Institution - 001-850-E
    • San Jose, California, United States, 95119
      • Local Institution - 001-850-F
    • San Leandro, California, United States, 94577
      • Local Institution - 001-850-A
    • Santa Barbara, California, United States, 93105
      • Local Institution - 001-884
    • Santa Clara, California, United States, 95051
      • Local Institution - 001-850-I
    • Solvang, California, United States, 93463
      • Local Institution - 001-884-A
    • Vallejo, California, United States, 94589
      • Local Institution - 001-850
    • Walnut Creek, California, United States, 94596
      • Local Institution - 001-850-G
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Local Institution - 001-872
    • Aurora, Colorado, United States, 80045
      • Local Institution - 001-810
    • Boulder, Colorado, United States, 80303
      • Local Institution - 001-872-H
    • Colorado Springs, Colorado, United States, 80907
      • Local Institution - 001-872-E
    • Colorado Springs, Colorado, United States, 80920
      • Local Institution - 001-872-L
    • Denver, Colorado, United States, 80218
      • Local Institution - 001-872-B
    • Denver, Colorado, United States, 80218
      • Local Institution - 001-951 - A
    • Denver, Colorado, United States, 80218
      • Local Institution - 001-951 - B
    • Grand Junction, Colorado, United States, 81501
      • Local Institution - 001-846
    • Lafayette, Colorado, United States, 80026
      • Local Institution - 001-951
    • Lakewood, Colorado, United States, 80228
      • Local Institution - 001-872-A
    • Littleton, Colorado, United States, 80218
      • Local Institution - 001-872-D
    • Lone Tree, Colorado, United States, 80124
      • Local Institution - 001-872-K
    • Longmont, Colorado, United States, 80501
      • Local Institution - 001-872-C
    • Parker, Colorado, United States, 80138
      • Local Institution - 001-872-J
    • Pueblo, Colorado, United States, 81008
      • Local Institution - 001-872-F
    • Pueblo, Colorado, United States, 81008
      • Local Institution - 001-872-G
    • Thornton, Colorado, United States, 80260
      • Local Institution - 001-872-I
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Local Institution - 001-816
  • Delaware
    • Newark, Delaware, United States, 19713-2055
      • Local Institution - 001-871
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Local Institution - 001-929i
    • Boca Raton, Florida, United States, 33432
      • Local Institution - 001-839
    • Bonita Springs, Florida, United States, 34135
      • Local Institution - 001-922A
    • Bradenton, Florida, United States, 34211
      • Local Institution - 001-922D
    • Brandon, Florida, United States, 33511
      • Local Institution - 001-929c
    • Cape Coral, Florida, United States, 33909
      • Local Institution - 001-922E
    • Clearwater, Florida, United States, 33761
      • Local Institution - 001-929g
    • Daytona Beach, Florida, United States, 32117
      • Local Institution - 001-926b
    • Fort Myers, Florida, United States, 33901
      • Local Institution - 001-922
    • Fort Myers, Florida, United States, 33905
      • Local Institution - 001-922B
    • Fort Myers, Florida, United States, 33908
      • Local Institution - 001-922C
    • Gainesville, Florida, United States, 32605
      • Local Institution - 001-929b
    • Jacksonville, Florida, United States, 32224
      • Local Institution - 001-829
    • Lady Lake, Florida, United States, 32159
      • Local Institution - 001-929m
    • Largo, Florida, United States, 33770
      • Local Institution - 001-929e
    • Lecanto, Florida, United States, 34461
      • Local Institution - 001-929n
    • Miami, Florida, United States, 33176
      • Local Institution - 001-870
    • Miami Beach, Florida, United States, 33140
      • Local Institution - 001-825
    • Naples, Florida, United States, 34102
      • Local Institution - 001-922F
    • Naples, Florida, United States, 34102
      • Local Institution - 001-922G
    • Ocala, Florida, United States, 34474
      • Local Institution - 001-538
    • Ocala, Florida, United States, 34474
      • Local Institution - 001-929p
    • Orange City, Florida, United States, 32763
      • Local Institution - 001-914
    • Orange City, Florida, United States, 32763
      • Local Institution - 001-929j
    • Orlando, Florida, United States, 32806
      • Local Institution - 001-929l
    • Pensacola, Florida, United States, 32503
      • Local Institution - 001-877
    • Port Charlotte, Florida, United States, 33980
      • Local Institution - 001-922H
    • Sarasota, Florida, United States, 34232
      • Local Institution - 001-922I
    • Sarasota, Florida, United States, 34236
      • Local Institution - 001-922J
    • Spring Hill, Florida, United States, 34608
      • Local Institution - 001-929h
    • St. Petersburg, Florida, United States, 33705
      • Local Institution - 001-929a
    • St. Petersburg, Florida, United States, 33705
      • Local Institution - 001-929
    • Stuart, Florida, United States, 34994
      • Local Institution - 001-926d
    • Tampa, Florida, United States, 33607
      • Local Institution - 001-929d
    • Tavares, Florida, United States, 32778
      • Local Institution - 001-929k
    • Trinity, Florida, United States, 34655
      • Local Institution - 001-929f
    • Venice, Florida, United States, 34285
      • Local Institution - 001-922K
    • Venice, Florida, United States, 34292
      • Local Institution - 001-922L
    • Vero Beach, Florida, United States, 32960
      • Local Institution - 001-926c
    • Wellington, Florida, United States, 33414
      • Local Institution - 001-926a
    • West Palm Beach, Florida, United States, 33401
      • Local Institution - 001-926
    • Winter Park, Florida, United States, 32789
      • Local Institution - 001-929o
  • Georgia
    • Athens, Georgia, United States, 30607
      • Local Institution - 001-967
    • Austell, Georgia, United States, 30106
      • Local Institution - 001-835-C
    • Austell, Georgia, United States, 30106
      • Local Institution - 001-835-E
    • Carrollton, Georgia, United States, 30117
      • Local Institution - 001-835-D
    • Carrollton, Georgia, United States, 30117
      • Local Institution - 001-835-F
    • Cartersville, Georgia, United States, 30121
      • Local Institution - 001-835-A
    • Douglasville, Georgia, United States, 30134
      • Local Institution - 001-835-B
    • Marietta, Georgia, United States, 30060
      • Local Institution - 001-835
  • Illinois
    • Chicago Ridge, Illinois, United States, 60415
      • Local Institution - 001-862
    • Niles, Illinois, United States, 60714
      • Local Institution - 001-883
  • Indiana
    • South Bend, Indiana, United States, 46601
      • Local Institution - 001-781
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Local Institution - 001-831
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Local Institution - 001-820
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Local Institution - 001-844
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Local Institution - 001-920
  • Maine
    • Biddeford, Maine, United States, 04005
      • Local Institution - 001-827
  • Maryland
    • Brandywine, Maryland, United States, 20613
      • Local Institution - 001-881-B
    • Columbia, Maryland, United States, 21044
      • Local Institution - 001-881
    • Silver Spring, Maryland, United States, 20904
      • Local Institution - 001-881-A
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 001-808
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Local Institution - 001-842
    • Detroit, Michigan, United States, 48202
      • Local Institution - 001-811
    • Farmington Hills, Michigan, United States, 48334
      • Local Institution - 001-842-A
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Local Institution - 001-838-F
    • Edina, Minnesota, United States, 55435
      • Local Institution - 001-838-E
    • Edina, Minnesota, United States, 55435
      • Local Institution - 001-875 - D
    • Maplewood, Minnesota, United States, 55109
      • Local Institution - 001-838-D
    • Maplewood, Minnesota, United States, 55109
      • Local Institution - 001-875 - A
    • Minneapolis, Minnesota, United States, 55404
      • Local Institution - 001-838-C
    • Minneapolis, Minnesota, United States, 55404
      • Local Institution - 001-875
    • Minneapolis, Minnesota, United States, 55415
      • Local Institution - 001-838-G
    • Minneapolis, Minnesota, United States, 55455
      • Local Institution - 001-822-A
    • Minneapolis, Minnesota, United States, 55455
      • Local Institution - 001-822
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 001-830
    • Saint Louis Park, Minnesota, United States, 55416
      • Local Institution - 001-838
    • Saint Louis Park, Minnesota, United States, 55426-5000
      • Local Institution - 001-838-B
    • Saint Paul, Minnesota, United States, 55101
      • Local Institution - 001-838-A
    • Saint Paul, Minnesota, United States, 55102
      • Local Institution - 001-875 - B
    • Woodbury, Minnesota, United States, 55125
      • Local Institution - 001-875 - C
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Local Institution - 001-952
    • Jefferson City, Missouri, United States, 65109
      • Local Institution - 001-950
  • Montana
    • Billings, Montana, United States, 59102
      • Local Institution - 001-841
  • Nebraska
    • Omaha, Nebraska, United States, 68105-1850
      • Local Institution - 001-544B
    • Omaha, Nebraska, United States, 68114
      • Local Institution - 001-959
    • Omaha, Nebraska, United States, 68118
      • Local Institution - 001-544A
    • Omaha, Nebraska, United States, 68198
      • Local Institution - 001-544
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Local Institution - 001-860A
    • Henderson, Nevada, United States, 89052
      • Local Institution - 001-860C
    • Henderson, Nevada, United States, 89074
      • Local Institution - 001-860B
    • Henderson, Nevada, United States, 89074
      • Local Institution - 001-860
    • Las Vegas, Nevada, United States, 89128
      • Local Institution - 001-860E
    • Las Vegas, Nevada, United States, 89144
      • Local Institution - 001-860D
    • Las Vegas, Nevada, United States, 89148
      • Local Institution - 001-860F
  • New York
    • Albany, New York, United States, 12206
      • Local Institution - 001-861
    • Buffalo, New York, United States, 14203
      • Local Institution - 001-815
    • New York, New York, United States, 10016
      • Local Institution - 001-813
    • New York, New York, United States, 10065
      • Local Institution - 001-806
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Local Institution - 001-812
    • Pinehurst, North Carolina, United States, 28374
      • Local Institution - 001-971
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Local Institution - 001-966
    • Cincinnati, Ohio, United States, 45267
      • Local Institution - 001-823
    • Cleveland, Ohio, United States, 44195
      • Local Institution - 001-818
    • Columbus, Ohio, United States, 43201
      • Local Institution - 001-833 - H
    • Columbus, Ohio, United States, 43203
      • Local Institution - 001-833 - C
    • Columbus, Ohio, United States, 43203
      • Local Institution - 001-833 - J
    • Columbus, Ohio, United States, 43210
      • Local Institution - 001-833 - A
    • Columbus, Ohio, United States, 43210
      • Local Institution - 001-833 - F
    • Columbus, Ohio, United States, 43210
      • Local Institution - 001-833
    • Columbus, Ohio, United States, 43212
      • Local Institution - 001-833 - D
    • Columbus, Ohio, United States, 43212
      • Local Institution - 001-833 - I
    • Columbus, Ohio, United States, 43219
      • Local Institution - 001-930
    • Columbus, Ohio, United States, 43221
      • Local Institution - 001-833 - B
    • Columbus, Ohio, United States, 43221
      • Local Institution - 001-833 - G
    • Gahanna, Ohio, United States, 43230
      • Local Institution - 001-833 - E
    • Kettering, Ohio, United States, 45429
      • Local Institution - 001-836-A
    • Kettering, Ohio, United States, 45429
      • Local Institution - 001-836
  • Oklahoma
    • Lawton, Oklahoma, United States, 73505
      • Local Institution - 001-600
    • Tulsa, Oklahoma, United States, 74146
      • Local Institution - 001-584
  • Oregon
    • Bend, Oregon, United States, 97701
      • Local Institution - 001-586-A
    • Bend, Oregon, United States, 97701
      • Local Institution - 001-586
    • Eugene, Oregon, United States, 97401
      • Local Institution - 001-889
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Local Institution - 001-837
    • Bethlehem, Pennsylvania, United States, 18017
      • Local Institution - 001-837-A
    • Hershey, Pennsylvania, United States, 17033-0850
      • Local Institution - 001-817
    • Media, Pennsylvania, United States, 19063
      • Local Institution - 001-783
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Local Institution - 001-887
    • Charleston, South Carolina, United States, 29425
      • Local Institution - 001-819
  • Tennessee
    • Gallatin, Tennessee, United States, 37066
      • Local Institution - 001-801-G
    • Hendersonville, Tennessee, United States, 37075
      • Local Institution - 001-801-A
    • Hermitage, Tennessee, United States, 37076
      • Local Institution - 001-801-D
    • Murfreesboro, Tennessee, United States, 37129
      • Local Institution - 001-801-F
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 001-801-B
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 001-801
    • Nashville, Tennessee, United States, 37207
      • Local Institution - 001-801-E
    • Nashville, Tennessee, United States, 37211
      • Local Institution - 001-801-C
  • Texas
    • Arlington, Texas, United States, 76012
      • Local Institution - 001-888-B
    • Arlington, Texas, United States, 76012
      • Local Institution - 001-888
    • Austin, Texas, United States, 78731
      • Local Institution - 001-880
    • Conroe, Texas, United States, 77384
      • Local Institution - 001-848a
    • Dallas, Texas, United States, 75230
      • Local Institution - 001-809
    • Dallas, Texas, United States, 75231
      • Local Institution - 001-886
    • Dallas, Texas, United States, 75246
      • Local Institution - 001-879
    • Denison, Texas, United States, 75020
      • Local Institution - 001-785
    • Fort Worth, Texas, United States, 76104
      • Local Institution - 001-876
    • Houston, Texas, United States, 77030
      • Local Institution - 001-848
    • Houston, Texas, United States, 77030
      • Local Institution - 001-969
    • Houston, Texas, United States, 77090
      • Local Institution - 001-935A
    • Irving, Texas, United States, 75063
      • Local Institution - 001-999
    • Kingwood, Texas, United States, 77339
      • Local Institution - 001-935D
    • Kingwood, Texas, United States, 77339
      • Local Institution - 001-935
    • Midland, Texas, United States, 79701
      • Local Institution - 001-554
    • San Antonio, Texas, United States, 78229
      • Local Institution - 001-802
    • Shenandoah, Texas, United States, 77380
      • Local Institution - 001-935B
    • Spring, Texas, United States, 77389
      • Local Institution - 001-935C
    • Sugar Land, Texas, United States, 77479
      • Local Institution - 001-874
    • Tomball, Texas, United States, 77375
      • Local Institution - 001-935E
    • Tyler, Texas, United States, 75702
      • Local Institution - 001-878
    • Waco, Texas, United States, 76712
      • Local Institution - 001-890
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Local Institution - 001-814
    • Fredericksburg, Virginia, United States, 24408
      • Local Institution - 001-597
    • Newport News, Virginia, United States, 23606
      • Local Institution - 001-882
    • Norfolk, Virginia, United States, 23502
      • Local Institution - 001-882-A
    • Norfolk, Virginia, United States, 23502
      • Local Institution - 001-890-A
    • Richmond, Virginia, United States, 23229
      • Local Institution - 001-968
  • Washington
    • Seattle, Washington, United States, 98109
      • Local Institution - 001-824
    • Vancouver, Washington, United States, 98684
      • Local Institution - 001-885
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Local Institution - 001-804

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation
• Unresectable or metastatic disease
• Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts
• Adequate organ function

Exclusion Criteria:

• History of intestinal disease or major gastric surgery or inability to swallow oral medications
• Other active cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Dose Exploration; Dose escalation of MRTX849 to determine maximum tolerated dose	Drug: MRTX849; MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental: Phase 1b Expansion; Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens	Drug: MRTX849; MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental: Phase 2; Separate cohorts of patients stratified by histological diagnosis, prior treatment history or co-mutation status (e.g., STK11) for evaluation of clinical activity of MRTX849	Drug: MRTX849; MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental: Pilot Phase 1b Combination with Pembrolizumab; Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC	Drug: MRTX849; MRTX849 will be administered orally once or twice daily in a continuous regimen; Drug: Pembrolizumab; Pembrolizumab is administered as an intravenous infusion once every 3 weeks
Experimental: Pilot Phase 1b Combination with Cetuximab; Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC	Drug: MRTX849; MRTX849 will be administered orally once or twice daily in a continuous regimen; Drug: Cetuximab; Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental: Pilot Phase 1b Combination with Afatinib; Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC	Drug: MRTX849; MRTX849 will be administered orally once or twice daily in a continuous regimen; Drug: Afatinib; Afatinib will be administered orally once a day in a continuous regimen
Experimental: Phase 2 Combination with Cetuximab; Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC	Drug: MRTX849; MRTX849 will be administered orally once or twice daily in a continuous regimen; Drug: Cetuximab; Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental: Pilot Phase 1b Combination with Cetuximab in NSCLC; Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC	Drug: MRTX849; MRTX849 will be administered orally once or twice daily in a continuous regimen; Drug: Cetuximab; Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental: Pilot Phase 1b Combination with Cetuximab in PDAC; Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC)	Drug: MRTX849; MRTX849 will be administered orally once or twice daily in a continuous regimen; Drug: Cetuximab; Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation	Number of participants with treatment related adverse events	20 months
Evaluate the pharmacokinetics of MRTX849	Blood plasma concentration	20 months
Evaluate clinical activity/efficacy of MRTX849	Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)	20 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish maximum tolerated dose	Number of participants with dose limiting toxicity	12 months
Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents	Number of participants with dose limiting toxicity	12 months
Evaluate the pharmacokinetics of new MRTX849 oral formulations	Blood plasma concentration	6 months
Evaluate the pharmacokinetics of MRTX849 administered with food	Blood plasma concentration	6 months

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Janne PA, Riely GJ, Gadgeel SM, Heist RS, Ou SI, Pacheco JM, Johnson ML, Sabari JK, Leventakos K, Yau E, Bazhenova L, Negrao MV, Pennell NA, Zhang J, Anderes K, Der-Torossian H, Kheoh T, Velastegui K, Yan X, Christensen JG, Chao RC, Spira AI. Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRASG12C Mutation. N Engl J Med. 2022 Jul 14;387(2):120-131. doi: 10.1056/NEJMoa2204619. Epub 2022 Jun 3.
• Sabari JK, Velcheti V, Shimizu K, Strickland MR, Heist RS, Singh M, Nayyar N, Giobbie-Hurder A, Digumarthy SR, Gainor JF, Rajan AP, Nieblas-Bedolla E, Burns AC, Hallin J, Olson P, Christensen JG, Kurz SC, Brastianos PK, Wakimoto H. Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data from Patients with KRASG12C-Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2022 Aug 2;28(15):3318-3328. doi: 10.1158/1078-0432.CCR-22-0383.
• Ou SI, Janne PA, Leal TA, Rybkin II, Sabari JK, Barve MA, Bazhenova L, Johnson ML, Velastegui KL, Cilliers C, Christensen JG, Yan X, Chao RC, Papadopoulos KP. First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1). J Clin Oncol. 2022 Aug 10;40(23):2530-2538. doi: 10.1200/JCO.21.02752. Epub 2022 Feb 15.
• Awad MM, Liu S, Rybkin II, Arbour KC, Dilly J, Zhu VW, Johnson ML, Heist RS, Patil T, Riely GJ, Jacobson JO, Yang X, Persky NS, Root DE, Lowder KE, Feng H, Zhang SS, Haigis KM, Hung YP, Sholl LM, Wolpin BM, Wiese J, Christiansen J, Lee J, Schrock AB, Lim LP, Garg K, Li M, Engstrom LD, Waters L, Lawson JD, Olson P, Lito P, Ou SI, Christensen JG, Janne PA, Aguirre AJ. Acquired Resistance to KRASG12C Inhibition in Cancer. N Engl J Med. 2021 Jun 24;384(25):2382-2393. doi: 10.1056/NEJMoa2105281.
• Negrao MV, Spira AI, Heist RS, Janne PA, Pacheco JM, Weiss J, Gadgeel SM, Velastegui K, Yang W, Der-Torossian H, Christensen JG, Sabari JK. Intracranial Efficacy of Adagrasib in Patients From the KRYSTAL-1 Trial With KRASG12C-Mutated Non-Small-Cell Lung Cancer Who Have Untreated CNS Metastases. J Clin Oncol. 2023 Oct 1;41(28):4472-4477. doi: 10.1200/JCO.23.00046. Epub 2023 Jun 16.
• Bekaii-Saab TS, Yaeger R, Spira AI, Pelster MS, Sabari JK, Hafez N, Barve M, Velastegui K, Yan X, Shetty A, Der-Torossian H, Pant S. Adagrasib in Advanced Solid Tumors Harboring a KRASG12C Mutation. J Clin Oncol. 2023 Sep 1;41(25):4097-4106. doi: 10.1200/JCO.23.00434. Epub 2023 Apr 26.
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Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 18, 2018
• First Submitted That Met QC Criteria: December 19, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; Pancreatic Cancer; Colorectal Cancer; KRAS G12C; Metastatic Cancer; Colon Cancer; KRAS; Adagrasib; STK11 mutation
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Neoplasms by Site; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Colonic Diseases; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Quinazolines; Cetuximab; Afatinib; pembrolizumab; adagrasib
• Other Study ID Numbers: CA239-0008 (Other Identifier: Bristol-Myers Squibb Protocol ID); 849-001 (Other Identifier: Mirati Therapeutics Protocol ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No