Trial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)

March 25, 2026 updated by: Mirati Therapeutics Inc.

A Randomized Study of Two Dosing Regimens of Adagrasib in Patients With Previously Treated Non-Small Cell Lung Cancer With KRAS G12C Mutation

This study will evaluate the efficacy of two dosing regimens of adagrasib (600 mg BID versus 400 mg BID) in patients with NSCLC with KRAS G12C mutation.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

CA239-0012 is a phase 2 study of adagrasib monotherapy in which patients are randomized between two dosing regimens. The study will evaluate the efficacy of two dosing regimens of adagrasib (600 mg BID without regard to food versus 400 mg BID with food) in patients with NSCLC with KRAS G12C mutation and who have received prior treatment with a platinum-based regimen and immune checkpoint inhibitor therapy.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2

Expanded Access

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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • São Paulo, Brazil, 01509-900
        • Local Institution - 102
      • São Paulo, Brazil, 01509-900
        • Local Institution - 175
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 41950-640
        • Local Institution - 181
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
        • Local Institution - 177
    • Santa Catarina
      • Itajaí, Santa Catarina, Brazil, 88301-220
        • Local Institution - 182
    • São Paulo
      • Belo Horizonte, São Paulo, Brazil, 30360-680
        • Local Institution - 178
  • Croatia
    • City of Zagreb
      • Zagreb, City of Zagreb, Croatia, 10000
        • Local Institution - 527
    • Primorje-Gorski Kotar County
      • Rijeka, Primorje-Gorski Kotar County, Croatia, 51000
        • Local Institution - 529
  • France
      • Paris, France, 75014
        • Local Institution - 562
      • Quimper, France, 29000
        • Local Institution - 558
      • Saint-Mandé, France, 94163
        • Local Institution - 550
    • Auvergne-Rhône-Alpes
      • Grenoble, Auvergne-Rhône-Alpes, France
        • Local Institution - 559
    • Gironde
      • Pessac, Gironde, France, 33604
        • Local Institution - 556
    • Loire-Atlantique
      • Saint-Herblain, Loire-Atlantique, France, 44800
        • Local Institution - 553
    • Maine-et-Loire
      • Angers, Maine-et-Loire, France, 49933
        • Local Institution - 554
    • Morbihan
      • Lorient, Morbihan, France, 56322
        • Local Institution - 552
    • Pays de la Loire Region
      • Nantes, Pays de la Loire Region, France, 44093
        • Local Institution - 555
    • Poitou-Charentes
      • Poitiers, Poitou-Charentes, France, 86000
        • Local Institution - 557
    • Provence-Alpes-Côte d'Azur Region
      • Nice, Provence-Alpes-Côte d'Azur Region, France, 06000
        • Local Institution - 561
    • Rhône
      • Marseille, Rhône, France, 13915
        • Local Institution - 551
      • Villefranche-sur-Saône, Rhône, France, 69655
        • Local Institution - 560
  • Greece
      • Thessaloniki, Greece, 54639
        • Local Institution - 576
      • Thessaloniki, Greece, 56429
        • Local Institution - 581
    • Achaïa
      • Pátrai, Achaïa, Greece, 265 04
        • Local Institution - 577
    • Attica
      • Athens, Attica, Greece, 11528
        • Local Institution - 575
    • North Aegean
      • Thessaloniki, North Aegean, Greece, 552 36
        • Local Institution - 580
    • Pella
      • Haidari - Athens, Pella, Greece, 12462
        • Local Institution - 579
  • Israel
      • Haifa, Israel, 3109601
        • Local Institution - 627
      • Tel Aviv, Israel, 6423906
        • Local Institution - 626
    • Jerusalem
      • Jerusalem, Jerusalem, Israel, 9103102
        • Local Institution - 625
    • Tel Aviv
      • Haifa, Tel Aviv, Israel, 31048
        • Local Institution - 629
      • Tel Aviv, Tel Aviv, Israel, 64239
        • Local Institution - 628
  • Italy
      • Milan, Italy, 20141
        • Local Institution - 779
      • Perugia, Italy, 6132
        • Local Institution - 775
      • Roma, Italy, 00144
        • Local Institution - 776
    • Pesaro E Urbino
      • Pesaro, Pesaro E Urbino, Italy, 61122
        • Local Institution - 778
    • Piedmont
      • Novara, Piedmont, Italy, 28100
        • Local Institution - 777
    • Torino
      • Candiolo, Torino, Italy, 10060
        • Local Institution - 780
  • Japan
    • Ehime
      • Tōon, Ehime, Japan, 791-0295
        • Local Institution - 401
    • Hyôgo [Hyogo]
      • Nishinomiya, Hyôgo [Hyogo], Japan, 663-8501
        • Local Institution - 403
    • Tiba [Chiba]
      • Kashiwa, Tiba [Chiba], Japan, 277-8577
        • Local Institution - 402
    • Ôsaka [Osaka]
      • Osaka, Ôsaka [Osaka], Japan, 541-8567
        • Local Institution - 400
  • Mexico
      • Toluca, Mexico, 50090
        • Local Institution - 125
    • Mexico City
      • Colonia Nápoles, Mexico City, Mexico, 3810
        • Local Institution - 129
      • Colonia Roma, Mexico City, Mexico, 06760
        • Local Institution - 127
  • Netherlands
      • Utrecht, Netherlands, 3543 AZ
        • Local Institution - 801
    • North Holland
      • Amsterdam, North Holland, Netherlands, 1066 CX
        • Local Institution - 800
  • Poland
      • Lublin, Poland, 20-064
        • Local Institution - 653
    • Lesser Poland Voivodeship
      • Krakow, Lesser Poland Voivodeship, Poland, 30-727
        • Local Institution - 650
    • Pomeranian Voivodeship
      • Gdynia, Pomeranian Voivodeship, Poland, 81-519
        • Local Institution - 651
  • Romania
      • Iași, Romania, 700106
        • Local Institution - 733
      • Sibiu, Romania, 550245
        • Local Institution - 725
      • Suceava, Romania, 720214
        • Local Institution - 728
    • Cluj
      • Cluj-Napoca, Cluj, Romania, 400641
        • Local Institution - 732
    • Constanța County
      • Ovidiu, Constanța County, Romania, 905900
        • Local Institution - 731
    • Dolj
      • Craiova, Dolj, Romania, 200385
        • Local Institution - 729
      • Craiova, Dolj, Romania, 200746
        • Local Institution - 734
    • Timiș County
      • Timișoara, Timiș County, Romania, 300166
        • Local Institution - 730
  • Serbia
    • Vojvodina
      • Nis, Vojvodina, Serbia, 11000
        • Local Institution - 754
    • Šumadijski Okrug
      • Kragujevac, Šumadijski Okrug, Serbia, 34000
        • Local Institution - 752
  • South Korea
    • Gyeonggido [Kyonggi-do]
      • Goyang-si, Gyeonggido [Kyonggi-do], South Korea, 10408
        • Local Institution - 327
    • Seoul Teugbyeolsi [Seoul-T'ukp
      • Seoul, Seoul Teugbyeolsi [Seoul-T'ukp, South Korea, 06273
        • Local Institution - 328
      • Seoul, Seoul Teugbyeolsi [Seoul-T'ukp, South Korea, 08308
        • Local Institution - 326
    • Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
      • Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], South Korea, 6351
        • Local Institution - 325
  • Spain
      • Barcelona, Spain, 08025
        • Local Institution - 683
      • Barcelona, Spain, 08028
        • Local Institution - 687
      • Barcelona, Spain, 08035
        • Local Institution - 681
      • Madrid, Spain, 28007
        • Local Institution - 675
      • Madrid, Spain, 28033
        • Local Institution - 679
      • Madrid, Spain, 28040
        • Local Institution - 688
      • Seville, Spain, 41009
        • Local Institution - 682
      • Valencia, Spain, 46010
        • Local Institution - 677
    • A Coruña
      • Santiago de Compostela, A Coruña, Spain, 15706
        • Local Institution - 680
    • Andalusia
      • Málaga, Andalusia, Spain, 29010
        • Local Institution - 678
    • Balearic Islands
      • Palma de Mallorca, Balearic Islands, Spain, 07120
        • Local Institution - 685
    • Principality of Asturias
      • Oviedo, Principality of Asturias, Spain, 33011
        • Local Institution - 676
  • Taiwan
    • Kaohsiung
      • Kaohsuing City, Kaohsiung, Taiwan, 833401
        • Local Institution - 352
    • Taichung
      • Taichung, Taichung, Taiwan, 402306
        • Local Institution - 353
      • Taichung, Taichung, Taiwan, 404327
        • Local Institution - 179
      • Taichung, Taichung, Taiwan, 404327
        • Local Institution - 350
  • Thailand
      • Khon Kaen, Thailand, 40002
        • Local Institution - 375
      • Songkhla, Thailand, 90110
        • Local Institution - 378
    • Chiang Mai
      • Muang, Chiang Mai, Thailand, 50200
        • Local Institution - 376
    • Krung Thep Maha Nakhon [Bangko
      • Bangkok, Krung Thep Maha Nakhon [Bangko, Thailand, 10700
        • Local Institution - 377
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye), 06200
        • Local Institution - 704
      • Ankara, Turkey (Türkiye), 06680
        • Local Institution - 701
      • Ankara, Turkey (Türkiye), 06800
        • Local Institution - 706
      • Edirne, Turkey (Türkiye), 22030
        • Local Institution - 700
      • Istanbul, Turkey (Türkiye), 34722
        • Local Institution - 707
      • Izmir, Turkey (Türkiye), 35100
        • Local Institution - 708
    • Ankara/Cankaya
      • Ankara, Ankara/Cankaya, Turkey (Türkiye), 06520
        • Local Institution - 705
    • Etlik/Ankara
      • Ankara, Etlik/Ankara, Turkey (Türkiye), 06010
        • Local Institution - 702
    • Samsun
      • Istanbul, Samsun, Turkey (Türkiye), 34214
        • Local Institution - 709
      • Istanbul, Samsun, Turkey (Türkiye), 34846
        • Local Institution - 710
  • United States
    • California
      • Santa Rosa, California, United States, 95403
        • Local Institution - 101
    • Missouri
      • Kansas City, Missouri, United States, 64128
        • Local Institution - 105
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Local Institution - 100
    • Texas
      • Dallas, Texas, United States, 75216-7167
        • Local Institution - 106

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Are at least 18 years old (or old enough to legally make their own treatment decisions, according to local laws).
  • Have advanced NSCLC or metastatic NSCLC (NSCLC that started in the lungs and then spread to other parts of the body) with the KRAS G12C mutation.
  • Have had previous treatment with 1) chemotherapy that included a drug called cisplatin or a drug called carboplatin and 2) a type of drug called an immune checkpoint inhibitor.
  • Have recovered from their prior treatment and blood tests are within a safe range.

Key Exclusion Criteria:

  • Have had previous treatment with a drug that targets KRAS G12C.
  • Have cancer that can potentially be removed with surgery.
  • Patients with brain lesions are not eligible if 1) any untreated brain lesions are > 2.0 cm in size 2) any brainstem lesions are present 3) ongoing steroid dosing >10 mg daily prednisone (or equivalent) and 4) poorly controlled (> 1/week) generalized or complex partial seizures or neurologic progression/instability due to brain lesions.
  • Have certain medical conditions or need to take certain medications that, in the opinion of a trial doctor, could make it unsafe for them to participate or difficult to complete the trial assessments, or are pregnant.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Adagrasib 600mg BID
Adagrasib 600mg BID without regard to food
Drug: Adagrasib
KRAS G12C inhibitor
Other Names:
  • MRTX849
  • Krazati
Experimental: Adagrasib 400mg BID
Adagrasib 400mg BID with food
Drug: Adagrasib
KRAS G12C inhibitor
Other Names:
  • MRTX849
  • Krazati

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Time Frame: 30 months
ORR evaluation of subjects treated with adagrasib 600 mg BID without regard to food versus 400 mg BID with food having NSCLC with KRAS G12C mutation (Study Population) will be completed per blinded independent central radiology (BICR) review. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from 1st dose of adagrasib until last dose of adagrasib.
30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate Overall Survival (OS).
Time Frame: 45 months
Overall survival is defined as time from date of randomization to date of death due to any cause.
45 months
Evaluate Progression Free Survival (PFS).
Time Frame: 30 months
Progression-free survival is defined as time from date of randomization to date of first progression per RECIST 1.1 or death from any cause, whichever occurs first.
30 months
Evaluate Duration of Response (DOR).
Time Frame: 30 months
Duration of response defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either PD (per BICR review) or death due to any cause, whichever occurs first.
30 months
Safety and tolerability in the study population.
Time Frame: 30 months

Safety characterized by number of participants with AEs, with abnormal laboratory test results and number of patients modifying or discontinuing study treatment due to an AE:

  1. Type, incidence, severity, timing, seriousness, and relationship to study treatment of Adverse Events.
  2. Laboratory abnormalities as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment.
  3. Number of patients modifying or discontinuing study treatment due to Adverse Event.
30 months
Population pharmacokinetic (PK) Model Derived Area Under the Curve During the Dosing Interval at Steady State (AUCtau,ss).
Time Frame: Pre-dose and 4-6 hours post dose; up to 6 months.
Sparse concentration data from this study will be pooled with other studies and analyzed using population PK methods to derive individual exposure parameters. Data for this Outcome Measure will not be reported here since ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Pre-dose and 4-6 hours post dose; up to 6 months.
Patient-reported symptoms during adagrasib administration from first dose to 28 days after last dose of adagrasib.
Time Frame: 30 months
Patient reported outcomes (PROs) will be used to assess symptomatic toxicity of adagrasib using the NCI Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Measurement System. PRO items reflect the specific symptom 1) frequency, severity, interference with usual or daily activities, 2) amount, or 3) presence or absence. PRO-CTCAE responses are scored from 0 (low) to 4 (high), or 0/1 for absent/present, and scores for each attribute (frequency, severity and/or interference) are presented descriptively.
30 months
Patient -reported quality of life during adagrasib administration from first dose to End of Treatment visit.
Time Frame: 30 months
Patient reported quality of life questionnaire will be used to assess five dimensions of patient health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using the 5-Level EQ-5D version (EQ-5D-5L) established by the EuroQol Group. This is presented descriptively, and patient responses correspond to a value of 1 (low) or 5 (high). Additionally, a one- page Visual Analog Scale (VAS) will be provided to patients so they may report their self-rated health from the best (100) and worst (0) health imaginable.
30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mirati Therapeutics Inc.

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 16, 2024

Primary Completion (Estimated)

July 30, 2026

Study Completion (Estimated)

July 30, 2026

Study Registration Dates

First Submitted

April 12, 2023

First Submitted That Met QC Criteria

May 2, 2023

First Posted (Actual)

May 10, 2023

Study Record Updates

Last Update Posted (Actual)

March 27, 2026

Last Update Submitted That Met QC Criteria

March 25, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA239-0012 (Other Identifier: Bristol-Myers Squibb Protocol ID)
  • 849-021 (Other Identifier: Mirati Therapeutics Protocol ID)
  • 2023-503523-25 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

IPD Sharing Time Frame

See Plan Description

IPD Sharing Access Criteria

See Plan Description

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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