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

NCT05853575 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: CA239-00122023-503523-25849-021
• Study Type: interventional
• Target: 200
• Locations: 18 countries
• Sites: 98

Brief Summary

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.

Conditions

Advanced Cancer; Metastatic Cancer; Malignant Neoplasm of Lung

Keywords

KRAS G12C; Non-small cell lung cancer; Metastatic cancer; NSCLC

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

  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 Outcomes (7)

• Evaluate Overall Survival (OS).

  45 months

• Evaluate Progression Free Survival (PFS).

  30 months

• Evaluate Duration of Response (DOR).

  30 months

• Safety and tolerability in the study population.

  30 months

• Population pharmacokinetic (PK) Model Derived Area Under the Curve During the Dosing Interval at Steady State (AUCtau,ss).

  Pre-dose and 4-6 hours post dose; up to 6 months.

Study Arms (2)

Adagrasib 600mg BID

EXPERIMENTAL

Adagrasib 600mg BID without regard to food

Drug: Adagrasib

Adagrasib 400mg BID

EXPERIMENTAL

Adagrasib 400mg BID with food

Drug: Adagrasib

Interventions

Adagrasib DRUG

KRAS G12C inhibitor

Also known as: MRTX849, Krazati

Adagrasib 400mg BID; Adagrasib 600mg BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mirati Therapeutics Inc.: lead

Study Sites (98)

Local Institution - 101

Santa Rosa, California, 95403, United States

Location

Local Institution - 105

Kansas City, Missouri, 64128, United States

Location

Local Institution - 100

Durham, North Carolina, 27705, United States

Location

Local Institution - 106

Dallas, Texas, 75216-7167, United States

Location

Local Institution - 181

Salvador, Estado de Bahia, 41950-640, Brazil

Location

Local Institution - 177

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Local Institution - 182

Itajaí, Santa Catarina, 88301-220, Brazil

Location

Local Institution - 178

Belo Horizonte, São Paulo, 30360-680, Brazil

Location

Local Institution - 102

São Paulo, 01509-900, Brazil

Location

Local Institution - 175

São Paulo, 01509-900, Brazil

Location

Local Institution - 527

Zagreb, City of Zagreb, 10000, Croatia

Location

Local Institution - 529

Rijeka, Primorje-Gorski Kotar County, 51000, Croatia

Location

Local Institution - 559

Grenoble, Auvergne-Rhône-Alpes, 0, France

Location

Local Institution - 556

Pessac, Gironde, 33604, France

Location

Local Institution - 553

Saint-Herblain, Loire-Atlantique, 44800, France

Location

Local Institution - 554

Angers, Maine-et-Loire, 49933, France

Location

Local Institution - 552

Lorient, Morbihan, 56322, France

Location

Local Institution - 555

Nantes, Pays de la Loire Region, 44093, France

Location

Local Institution - 557

Poitiers, Poitou-Charentes, 86000, France

Location

Local Institution - 561

Nice, Provence-Alpes-Côte d'Azur Region, 06000, France

Location

Local Institution - 551

Marseille, Rhône, 13915, France

Location

Local Institution - 560

Villefranche-sur-Saône, Rhône, 69655, France

Location

Local Institution - 562

Paris, 75014, France

Location

Local Institution - 558

Quimper, 29000, France

Location

Local Institution - 550

Saint-Mandé, 94163, France

Location

Local Institution - 577

Pátrai, Achaïa, 265 04, Greece

Location

Local Institution - 575

Athens, Attica, 11528, Greece

Location

Local Institution - 580

Thessaloniki, North Aegean, 552 36, Greece

Location

Local Institution - 579

Haidari - Athens, Pella, 12462, Greece

Location

Local Institution - 576

Thessaloniki, 54639, Greece

Location

Local Institution - 581

Thessaloniki, 56429, Greece

Location

Local Institution - 625

Jerusalem, Jerusalem, 9103102, Israel

Location

Local Institution - 629

Haifa, Tel Aviv, 31048, Israel

Location

Local Institution - 628

Tel Aviv, Tel Aviv, 64239, Israel

Location

Local Institution - 627

Haifa, 3109601, Israel

Location

Local Institution - 626

Tel Aviv, 6423906, Israel

Location

Local Institution - 778

Pesaro, Pesaro E Urbino, 61122, Italy

Location

Local Institution - 777

Novara, Piedmont, 28100, Italy

Location

Local Institution - 780

Candiolo, Torino, 10060, Italy

Location

Local Institution - 779

Milan, 20141, Italy

Location

Local Institution - 775

Perugia, 6132, Italy

Location

Local Institution - 776

Roma, 00144, Italy

Location

Local Institution - 401

Tōon, Ehime, 791-0295, Japan

Location

Local Institution - 403

Nishinomiya, Hyôgo [Hyogo], 663-8501, Japan

Location

Local Institution - 402

Kashiwa, Tiba [Chiba], 277-8577, Japan

Location

Local Institution - 400

Osaka, Ôsaka [Osaka], 541-8567, Japan

Location

Local Institution - 129

Colonia Nápoles, Mexico City, 3810, Mexico

Location

Local Institution - 127

Colonia Roma, Mexico City, 06760, Mexico

Location

Local Institution - 125

Toluca, 50090, Mexico

Location

Local Institution - 800

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Local Institution - 801

Utrecht, 3543 AZ, Netherlands

Location

Local Institution - 650

Krakow, Lesser Poland Voivodeship, 30-727, Poland

Location

Local Institution - 651

Gdynia, Pomeranian Voivodeship, 81-519, Poland

Location

Local Institution - 653

Lublin, 20-064, Poland

Location

Local Institution - 732

Cluj-Napoca, Cluj, 400641, Romania

Location

Local Institution - 731

Ovidiu, Constanța County, 905900, Romania

Location

Local Institution - 729

Craiova, Dolj, 200385, Romania

Location

Local Institution - 734

Craiova, Dolj, 200746, Romania

Location

Local Institution - 730

Timișoara, Timiș County, 300166, Romania

Location

Local Institution - 733

Iași, 700106, Romania

Location

Local Institution - 725

Sibiu, 550245, Romania

Location

Local Institution - 728

Suceava, 720214, Romania

Location

Local Institution - 754

Nis, Vojvodina, 11000, Serbia

Location

Local Institution - 752

Kragujevac, Šumadijski Okrug, 34000, Serbia

Location

Local Institution - 327

Goyang-si, Gyeonggido [Kyonggi-do], 10408, South Korea

Location

Local Institution - 325

Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], 6351, South Korea

Location

Local Institution - 328

Seoul, Seoul Teugbyeolsi [Seoul-T'ukp, 06273, South Korea

Location

Local Institution - 326

Seoul, Seoul Teugbyeolsi [Seoul-T'ukp, 08308, South Korea

Location

Local Institution - 680

Santiago de Compostela, A Coruña, 15706, Spain

Location

Local Institution - 678

Málaga, Andalusia, 29010, Spain

Location

Local Institution - 685

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Local Institution - 676

Oviedo, Principality of Asturias, 33011, Spain

Location

Local Institution - 683

Barcelona, 08025, Spain

Location

Local Institution - 687

Barcelona, 08028, Spain

Location

Local Institution - 681

Barcelona, 08035, Spain

Location

Local Institution - 675

Madrid, 28007, Spain

Location

Local Institution - 679

Madrid, 28033, Spain

Location

Local Institution - 688

Madrid, 28040, Spain

Location

Local Institution - 682

Seville, 41009, Spain

Location

Local Institution - 677

Valencia, 46010, Spain

Location

Local Institution - 352

Kaohsuing City, Kaohsiung, 833401, Taiwan

Location

Local Institution - 353

Taichung, Taichung, 402306, Taiwan

Location

Local Institution - 179

Taichung, Taichung, 404327, Taiwan

Location

Local Institution - 350

Taichung, Taichung, 404327, Taiwan

Location

Local Institution - 376

Muang, Chiang Mai, 50200, Thailand

Location

Local Institution - 377

Bangkok, Krung Thep Maha Nakhon [Bangko, 10700, Thailand

Location

Local Institution - 375

Khon Kaen, 40002, Thailand

Location

Local Institution - 378

Songkhla, 90110, Thailand

Location

Local Institution - 705

Ankara, Ankara/Cankaya, 06520, Turkey (Türkiye)

Location

Local Institution - 702

Ankara, Etlik/Ankara, 06010, Turkey (Türkiye)

Location

Local Institution - 709

Istanbul, Samsun, 34214, Turkey (Türkiye)

Location

Local Institution - 710

Istanbul, Samsun, 34846, Turkey (Türkiye)

Location

Local Institution - 704

Ankara, 06200, Turkey (Türkiye)

Location

Local Institution - 701

Ankara, 06680, Turkey (Türkiye)

Location

Local Institution - 706

Ankara, 06800, Turkey (Türkiye)

Location

Local Institution - 700

Edirne, 22030, Turkey (Türkiye)

Location

Local Institution - 707

Istanbul, 34722, Turkey (Türkiye)

Location

Local Institution - 708

Izmir, 35100, Turkey (Türkiye)

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Neoplasm Metastasis; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

adagrasib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: May 10, 2023
• Study Start: February 16, 2024
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

BR (6); TH (4); TU (10); ME (3); GR (6); KR (4); RO (8); IL (5); NL (2); SE (2); CR (2); TW (4); JP (4); US (4); ES (12); PL (3); FR (13); IT (6)