Clinical trial NCT05853575: Trial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)
Official title: A Randomized Study of Two Dosing Regimens of Adagrasib in Patients With Previously Treated Non-Small Cell Lung Cancer With KRAS G12C Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Cancer
Metastatic Cancer
Malignant Neoplasm of Lung
Keywords: KRAS G12C
Non-small cell lung cancer
Metastatic cancer
NSCLC
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2023-05-10
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
timeFrame: 30 months
Secondary outcomes:
measure: Evaluate Overall Survival (OS).
timeFrame: 45 months
measure: Evaluate Progression Free Survival (PFS).
timeFrame: 30 months
measure: Evaluate Duration of Response (DOR).
timeFrame: 30 months
measure: Safety and tolerability in the study population.
timeFrame: 30 months
measure: Population pharmacokinetic (PK) Model Derived Area Under the Curve During the Dosing Interval at Steady State (AUCtau,ss).
timeFrame: Pre-dose and 4-6 hours post dose; up to 6 months.
measure: Patient-reported symptoms during adagrasib administration from first dose to 28 days after last dose of adagrasib.
timeFrame: 30 months
measure: Patient -reported quality of life during adagrasib administration from first dose to End of Treatment visit.
timeFrame: 30 months
Other outcomes:
Locations:
city: Santa Rosa
country: United States
facility: Providence Medical Foundation - Research
state: California
city: Chicago
country: United States
facility: Local Institution - 104
state: Illinois
city: Minneapolis
country: United States
facility: Local Institution - 103
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City VA Hospital
state: Missouri
city: Durham
country: United States
facility: Veterans Affairs Medical Center (VAMC) - Durham - Oncology
state: North Carolina
city: Dallas
country: United States
facility: VA North Texas Healthcare System/Dallas VA Medical Center
state: Texas
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS
state: Rio Grande Do Sul
city: Itajaí
country: Brazil
facility: Clinica de Neoplasias Litoral
state: Santa Catarina
city: Belo Horizonte
country: Brazil
facility: Oncocentro Belo Horizonte
state: São Paulo
city: Salvador
country: Brazil
facility: AMO Assistencia Multidisciplinar em Oncologia
city: São Paulo
country: Brazil
facility: A.C. Camargo Cancer Center
city: São Paulo
country: Brazil
facility: A.C. Camargo Cancer Center
city: Zagreb
country: Croatia
facility: Klinički bolnički centar Sestre milosrdnice
state: Grad Zagreb
city: Pula
country: Croatia
facility: Local Institution - 525
state: Istarska Županija
city: Pessac
country: France
facility: Hopital Haut-Leveque - Maladies respiratoires
state: Gironde
city: Saint-Herblain Cedex
country: France
facility: Institut de Cancerologie de I'Ouest - Service d'Oncologie Medicale - Service d'Oncologie Médicale
state: Loire-Atlantique
city: Angers
country: France
facility: Centre Hospitalier Universitaire D' Angers Hôpital Larrey - PNEUMOLOGIE
state: Maine-et-Loire
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers - Service d'oncologie Médicale Oncologie Medicale - Cancerolo
state: Poitou-Charentes
city: Grenoble
country: France
facility: CHU de Grenoble
state: Rhône-Alpes
city: Marseille
country: France
facility: AP-HM Hopital Nord
state: Rhône
city: Villefranche Sur Saone
country: France
facility: Centre Hosptalier De Villefranche-Sur-Saone - Oncologie Medicale - Cancerolo
state: Rhône
city: Lorient
country: France
facility: Centre Hôspitalier de Bretagne Sud - Hôpital du Scorff
city: Nantes cedex 1
country: France
facility: CHU de Nantes - Hôpital Nord Laënnec (HGRL)
city: Quimper
country: France
facility: Centre Hospitalier de Cornouaille
city: Saint-Mandé
country: France
facility: Hôpital Bégin - Service d'Oncologie
city: Patra
country: Greece
facility: University of Patras
state: Achaïa
city: Athens
country: Greece
facility: General Hospital of Athens "Alexandra"
state: Attiki
city: Athens
country: Greece
facility: Local Institution - 582
state: Attiki
city: Haidari - Athens
country: Greece
facility: University General Hospital Attikon
state: Attiki
city: Panorama
country: Greece
facility: St. Luke's Hospital S.A.
city: Thessaloniki
country: Greece
facility: Theageneio Cancer Hospital
city: Thessaloniki
country: Greece
facility: General Hospital Of Thessaloniki Papageorgiou
city: Szolnok
country: Hungary
facility: Local Institution - 600
state: Jász-Nagykun-Szolnok
city: Haifa
country: Israel
facility: Bnai Zion Medical Center Rheumatology Unit
state: Tel-Aviv
city: Tel Aviv-Yafo
country: Israel
facility: Assuta Medical Center
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical center - Oncology
state: Yerushalayim
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Tel-Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center - Oncology - Hematology/Oncology
city: Pesaro
country: Italy
facility: Azienda Sanitaria Territoriale Pesaro Urbino (AST PU)
state: Pesaro E Urbino
city: Novara
country: Italy
facility: Azienda Ospedaliero-Universitaria Maggiore Della Carita
state: Piemonte
city: Candiolo
country: Italy
facility: Istituto di Candiolo, IRCCS
state: Torino
city: Milano
country: Italy
facility: IEO - Istituto Europeo di Oncologia, IRCCS
city: Perugia
country: Italy
facility: Ospedale S.Maria della Misericordia, AO di Perugia, Università degli Studi di Perugia
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena - IRCCS - IFO
city: Toon
country: Japan
facility: Local Institution - 401
state: Ehime
city: Nishinomiya
country: Japan
facility: Local Institution - 403
state: Hyôgo [Hyogo]
city: Goyang-Si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggido [Kyonggi-do]
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital - Oncology
state: Seoul Teugbyeolsi [Seoul-T'ukp
city: Tuxtla Gutiérrez
country: Mexico
facility: Local Institution - 128
state: Chiapas
city: Toluca
country: Mexico
facility: Local Institution - 125
city: Breda
country: Netherlands
facility: Local Institution - 802
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: Anthoni van Leeuwenhoek Ziekenhuis, Nederlands Kanker Instit
state: Noord-Holland
city: Utrecht
country: Netherlands
facility: St. Antonius Hospital
city: San Martin de Porres
country: Peru
facility: Local Institution - 152
state: Lima
city: Krakow
country: Poland
facility: Local Institution - 129
state: Malopolskie
city: Krakow
country: Poland
facility: Pratia MCM Krakow
state: Malopolskie
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o.o. - Oddzial Onkologii i Radioterapii - Oddzial Onkologii Klinicznej
state: Pomorskie
city: Lublin
country: Poland
facility: MS Pneumed Janusz Milanowski, Katarzyna Szmygin-Milanowska Sp. Jawna
city: Cluj-Napoca
country: Romania
facility: Medisprof - Medical Oncology
state: Cluj
city: Ovidiu
country: Romania
facility: Ovidius Clinical Hospital
state: Constanta
city: Craiova
country: Romania
facility: Local Institution - 727
state: Dolj
city: Craiova
country: Romania
facility: Oncolab - Medical Oncology
state: Dolj
city: Craiova
country: Romania
facility: Centrul de Oncologie Sf Nectarie - Medical Oncology
state: Dolj
city: Timisoara
country: Romania
facility: Oncocenter- Oncologie Clinica - Medical Oncology
state: Timis
city: Iasi
country: Romania
facility: Centrul de Oncologie Euroclinic
city: Sibiu
country: Romania
facility: Spitalul Clinic Judetean De Urgenta Sibiu
city: Suceava
country: Romania
facility: Local Institution - 127
city: Suceava
country: Romania
facility: Sigmedical Services S.R.L.
city: Nis
country: Serbia
facility: University Clinical Center of Nis, Clinic for Pediatrics-Department for Pulmonology
state: Vojvodina
city: Sremska Kamenica
country: Serbia
facility: Local Institution - 750
state: Vojvodina
city: Belgrade
country: Serbia
facility: Local Institution - 753
city: Belgrade
country: Serbia
facility: Local Institution - 751
city: Kragujevac
country: Serbia
facility: University Clinical Center of Kragujevac, Center for Internal Oncology
state: Šumadijski Okrug
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario De Santiago - Oncología Médica
state: A Coruña
city: Malaga
country: Spain
facility: Hospital Regional Universitario De Málaga
state: Andalucía
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Baleares
city: Santander
country: Spain
facility: Local Institution - 686
state: Cantabria
city: Valencia
country: Spain
facility: Local Institution - 684
state: Valenciana, Comunidad
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Dexeus Grupo Quironsalud
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - Oncología Médica
city: Barcelona
country: Spain
facility: Local Institution - 689
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón - Oncología Médica
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: M.D. Anderson Center Madrid
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de la Macarena - Oncología Médica
city: Valencia
country: Spain
facility: Hospital Clinico Universitario De Valencia - Oncologia Médica y Hematologia
city: Kaohsiung City
country: Taiwan
facility: Local Institution - 351
state: Kaohsiung
city: Taichung City
country: Taiwan
facility: China Medical University Hospital - Internal Medicine
state: Taichung Municipality
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University Hospital
state: Taichung
city: Taichung City
country: Taiwan
facility: China Medical University Hospital - Internal Medicine
state: Taichung
city: Taichung City
country: Taiwan
facility: Local Institution - 355
state: Taichung
city: Taipei City
country: Taiwan
facility: Local Institution - 354
state: Taipei
city: Muang
country: Thailand
facility: Local Institution - 376
state: Chiang Mai
city: Bangkok
country: Thailand
facility: Siriraj Hospital
state: Krung Thep Maha Nakhon [Bangkok]
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital - ACADEMIC CLINICAL RESEARCH OFFICE
city: Songkhla
country: Thailand
facility: Local Institution - 378
city: Istanbul
country: Turkey
facility: Local Institution - 703
state: Samsun
city: Ankara
country: Turkey
facility: Gulhane Training and Research Hospital - Medical Oncology
city: Ankara
country: Turkey
facility: Dr Abdurrahman Yurtaslan Training and Research Hospital - Medical Oncology
city: Ankara
country: Turkey
facility: Ankara Liv Hospital
city: Ankara
country: Turkey
facility: Ankara City Hospital - Medical Oncology
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi Tibbi Onkoloji
city: Edirne
country: Turkey
facility: Trakya Univ Hastanesi Ic Hastal
city: Istanbul
country: Turkey
facility: Medipol Mega Universite Hastanesi Tibbi Onkoloji
city: Istanbul
country: Turkey
facility: Goztepe SuleymanYalcin Sehir Hast
city: Istanbul
country: Turkey
facility: Istanbul Onkoloji Hastanesi Tibbi Onkoloji
city: Izmir
country: Turkey
facility: Ege University Medical Faculty - Pulmonary
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: