NCT04613596ClinicalTrials.gov

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

A Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

En recrutementAccepte des participants actuellement, selon la fiche du registre.

Contacter cette étude

En bref

Phase 2 / Phase 3626 participants recherchés770 sites47 pays

Catégories

Oncologie71%Respiratoire29%

Enregistré dans 1 registre

ClinicalTrials.govNCT04613596Ouvrir cette fiche sur ClinicalTrials.govSynchronisé il y a 5 jours

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How this study is set up

The points below are drawn from the public registry record for this study. Each one cites the field or sentence it came from. A dash (—) means the record does not state something — not that it is missing or wrong. Many well-run studies, especially small ones, leave some of these blank.

Present: Registered before enrolment beganFirst posted 2020-11-03; recorded start 2020-12-02
Present: Has a defined primary outcomeA primary outcome measure is listed in the record
Present: The primary outcome states a time frameThe primary outcome measure records a time frame
Present: Participants are randomly assignedAllocation is recorded as randomised
Present: Has a comparison groupThe record lists a placebo or comparator arm, or more than one study arm
Not stated: Open label (no blinding)Masking is recorded as none (open label)
Not stated: An ethics committee is not stated in the registry recordThis registry's ingested record has no ethics-committee field
Not stated: Regulatory oversight (such as an IND or IDE) is not stated in the registry recordThis registry's ingested record has no regulatory-authorisation field
Not stated: A data monitoring committee is not stated in the registry recordThis registry's ingested record has no data-monitoring-committee fieldA data monitoring committee is not required for many smaller studies, and its absence here is not unusual.
Present: No cost to participants is mentioned in the recordChecked the summary, description and eligibility text; no cost-to-participant phrase found
Present: Sponsor has 19 other studies in this databaseCounted from the lead sponsor named in the record (Mirati Therapeutics Inc.)
Present: Sponsor has posted results for at least one studyBased on the sponsor’s studies in this database

The record lists 2 conditions.
Lead sponsor type recorded as: industry.
Intervention regulatory context: investigational, within a phased regulatory pathway.

These are facts from the public registry record, not a judgement about the study. Discuss any trial with your own doctor before taking part.

What these facts mean, and what to ask · ruleset v1

Trial stature

Three independent measures of this study, described from its registry record — not a recommendation about it. A rigorous study by investigators nobody has heard of is better evidence than a weak study led by a famous one. How these are scored.

Methodological rigourSTRONG

A strong methodological design for a phase 3 study, judged from its ClinicalTrials.gov record.

How this score is built

Randomised allocation20/20
Participants are randomly allocated between arms
Blinding0/20
Open-label
Control arm15/15
Active-comparator control arm
Primary-outcome specificity10/10
Named primary outcome with a defined time frame
Endpoint type3/10
Surrogate or intermediate endpoint (conservative default)
Multi-centre8/8
Multi-centre: 770 sites
Data monitoring committee0/7
No data monitoring committee stated
Prospective registration5/5
Registered before the study start date
Protocol / SAP posted0/5
No protocol or SAP posted to the registry

ScaleMEDIUM

A medium-sized study, international in scope: 626 participants (target), run at 770 sites, across 47 countries.

How this score is built

Enrolment27/40
626 participants (target)
Site count25/25
770 sites
Country count15/15
47 countries
Planned duration10/10
Planned over about 109 months
Sponsor scale4/10
Mirati Therapeutics Inc. has led 19 trials in our corpus

Investigator standingUNKNOWN

We have no verifiable track record for the investigator named on this trial. That is common for early-career investigators and for records held outside ClinicalTrials.gov — it is not a negative signal.

How this score is built

Investigator standing0/100
No investigator recorded in the registry for this trial

These describe the registry record only, and today we hold ClinicalTrials.gov data. Absent fields lower a score, and absence often reflects registration practice rather than study quality. A high-stature trial is not necessarily safer or a better choice for you — enrolling in a large definitive trial can mean a higher chance of receiving placebo, while a small early-phase study may be the only route to a new therapy.

Résumé

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.

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.

Affections

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

Éligibilité

Éligibilité
Sexe	Tous
Âges	18 Years – Aucun maximum
Volontaires sains	Non

Éligibilité telle qu'elle figure dans le registre

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

Éligibilité en énoncés simples

Les critères de cette fiche n'ont pas encore été décomposés en énoncés distincts. Le texte du registre ci-dessus est complet et fait foi.

Conception de l'étude

Conception de l'étude
Type d'étude	Interventionnelle
Phase	Phase 2 / Phase 3
Répartition	Randomisée
Modèle d'intervention	PARALLEL
Objectif principal	TREATMENT
Insu	NONE (0)
Recrutement	626 participants recherchés

Promoteur et collaborateurs

Mirati Therapeutics Inc. Promoteur

Groupes et interventions

Phase 2 Cohort 1a: PD-L1 TPS <1%EXPERIMENTAL
Cohort 1a: Adagrasib twice daily (BID) in combination with pembrolizumab
Phase 2 Cohort 1b: PD-L1 TPS <1%EXPERIMENTAL
Cohort 1b: Adagrasib BID monotherapy
Phase 2 Cohort 2: PD-L1 TPS ≥1%EXPERIMENTAL
Cohort 2: Adagrasib BID in combination with pembrolizumab
Phase 3 Cohort 3 Investigational ArmEXPERIMENTAL
Adagrasib BID in combination with pembrolizumab
Phase 3 Cohort 4 Comparator ArmACTIVE_COMPARATOR
Pembrolizumab

Interventions

Médicament Adagrasib
Adagrasib 400 mg twice daily (BID) in combination with pembrolizumab (Cohort 1a)
Médicament Adagrasib
Adagrasib 600 mg BID monotherapy (Cohort 1b)
Médicament Adagrasib
adagrasib 400 mg BID in combination with pembrolizumab
Médicament Adagrasib
Adagrasib 400 mg BID + pembrolizumab 200 mg every Q3W
Médicament Pembrolizumab
Pembrolizumab 200 mg IV Q3W

Critères de jugement

Critère de jugement principal
Phase 2: To evaluate the efficacy of Adagrasib monotherapy and in combination with pembrolizumab administered to patients having advanced/metastatic NSCLC.
Objective Response Rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Délai 22 months
Critère de jugement principal
Phase 3: To compare efficacy of Adagrasib in combination with pembrolizumab versus pembrolizumab
Progression Free Survival per RECIST 1.1 by Blinded Independent Central Review (BICR) and Overall Survival
Délai 36 months
Critère de jugement secondaire
Phase 2: To characterize the safety and tolerability of study treatments in selected populations
Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities.
Délai 22 months
Critère de jugement secondaire
Phase 2: 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 Progression of Disease (PD) or death due to any cause, whichever occurs first.
Délai 22 months
Critère de jugement secondaire
Phase 2: Progression Free Survival
Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Délai 22 months
Critère de jugement secondaire
Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations
1-Year Survival rate
Délai 12 months
Critère de jugement secondaire
Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations
Overall Survival (OS)
Délai 22 months
Critère de jugement secondaire
Phase 2: To evaluate the pharmacokinetics (PK) of study treatments by measuring blood plasma MRTX849 and potential metabolite concentrations.
Pharmacokinetics (PK) Blood plasma Adagrasib and potential metabolite concentrations
Délai 22 months
Critère de jugement secondaire
Phase 3: To evaluate the safety and tolerability in the study population
Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities.
Délai 36 months
Critère de jugement secondaire
Phase 3: To evaluate health-related quality of life (HRQOL) and lung cancer specific symptoms in the study population
Patient Reported Outcomes to measure quality of life
Délai 36 months
Critère de jugement secondaire
Phase 3: Progression Free Survival per RECIST 1.1 by Investigator
Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Délai 36 months
Critère de jugement secondaire
Phase 3: Duration of Response (DOR) per RECIST 1.1 by Investigator and BICR
Defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first.
Délai 36 months
Critère de jugement secondaire
Phase 3: Objective Response Rate (ORR) per RECIST 1.1 by Investigator and BICR
Defined as the percent of patients documented to have a confirmed CR or PR.
Délai 36 months

Dates

Dates
Date de début	2 décembre 2020 (réelle)
Achèvement principal	31 octobre 2028 (estimée)
Achèvement	31 octobre 2029 (estimée)
Première publication	3 novembre 2020 (réelle)
Dernière mise à jour	16 septembre 2026
Résultats publiés	Non précisé dans la fiche du registre
Statut vérifié pour la dernière fois	septembre 2026

Réelle signifie que l'événement a eu lieu. Estimée signifie que le promoteur s'y attend. Les deux ont un sens différent.

Lieux

378 sites sont en recrutement

Argentina

Argentina
Établissement	Ville	État ou région	Statut
Aresma - Clinica Adventista Belgrano	Belgrano	Buenos Aires	En recrutement
Local Institution - 007-5002	Buenos Aires		Pas encore en recrutement
Instituto Medico Especializado Alexander Fleming	Buenos Aires		En recrutement
Instituto Argentino de Diagnostico y Tratamiento	Ciudad Autonoma de Buenos Aires	Buenos Aires	En recrutement
Fundacion Respirar	Ciudad Autonoma de Buenos Aires	Buenos Aires	En recrutement
Local Institution - Unk043	Ciudad Autonoma de Buenos Aires	Buenos Aires	Actif, sans recrutement
Instituto Oncologico de Cordoba (IONC)	Córdoba		En recrutement
Local Institution - 007-436	Pergamino	Buenos Aires	Pas encore en recrutement
Local Institution - Unk033	Porto Alegre		Actif, sans recrutement
Sanatorio Parque	Rosario	Santa Fe Province	En recrutement
Instituto de Oncologia de Rosario	Rosario	Santa Fe Province	En recrutement
Local Institution - Unk020	Río Cuarto		Actif, sans recrutement
Centro Oncologico Korben	San Pedro	Buenos Aires	En recrutement
Local Institution - 007-433	Viedma		Pas encore en recrutement

Australia

Australia
Établissement	Ville	Statut
Ballarat Regional Integrated Cancer Center	Ballarat	En recrutement
Flinders Medical Centre	Bedford Park	En recrutement
Local Institution - 007-004	Clayton	Retiré
Canberra Hospital	Garran	En recrutement
Icon Cancer Centre	Hyde Park	En recrutement
Port Macquarie Base Hospital	Port Macquarie	En recrutement
Cancer Care Wollongong	Wollongong	En recrutement
Princess Alexandra Hospital	Woolloongabba	En recrutement

Austria

Austria
Établissement	Ville	Statut
Klinikum Klagenfurt Am Worthersee	Klagenfurt	En recrutement
Universitatsklinikum Krems	Krems	En recrutement
Ordensklinikum Linz Elisabethinen	Linz	En recrutement
Wiener Gesundheitsverbund - Klinik Hietzing	Vienna	En recrutement
Wiener Gesundheitsverbund - Klinik Floridsdorf	Vienna	En recrutement
Medizinische Universitat Wien	Vienna	En recrutement

Belgium

Belgium
Établissement	Ville	Statut
Universitair Ziekenhuis Antwerpen	Edegem	En recrutement
Algemeen Ziekenhuis Maria Middelares	Ghent	En recrutement
Jessa Ziekenhuis - Campus Virga Jesse	Hasselt	En recrutement
Local Institution - 007-152	Roeselare	Retiré

Brazil

Brazil
Établissement	Ville	État ou région	Statut
Local Institution - Unk060	Barretos		Actif, sans recrutement
Fundacao Pio XII - Hospital de Cancer de Barretos - Hospital de Amor	Barretos		En recrutement
CEPON - Centro de Pesquisas Oncologicas	Florianópolis	Santa Catarina	En recrutement
Local Institution - Unk002	Ijuí		Actif, sans recrutement
Local Institution - Unk050	Lajeado	Rio Grande do Sul	Actif, sans recrutement
Liga Contra o Cancer - Centro Avancado de Oncologia	Natal	Rio Grande do Norte	En recrutement
Local Institution - 007-5052	Porto Alegre	Rio Grande do Sul	Pas encore en recrutement
Local Institution - Unk015	Porto Alegre	Rio Grande do Sul	Actif, sans recrutement
Hospital Nossa Senhora da Conceicao	Porto Alegre		En recrutement
Local Institution - Unk003	Rio de Janeiro		Actif, sans recrutement
Hospital Santa Izabel	Salvador	Estado de Bahia	En recrutement
Local Institution - Unk019	São José do Rio Preto		Actif, sans recrutement
Local Institution - Unk074	São Paulo		Actif, sans recrutement

Bulgaria

Bulgaria
Établissement	Ville	Statut
Multiprofile Hospital For Active Treatment - Dr. Tota Venkova	Gabrovo	En recrutement
Specialized Hospital for Active Oncology Treatment - Haskovo SLLC (SBALO - Haskovo - EOOD)	Haskovo	En recrutement
Complex Oncology Center - Plovdiv - Base II	Plovdiv	En recrutement
University Multiprofile Hospital for Active Treatment St. Ivan Rilski	Sofia	En recrutement
Complex Oncology Center - Vratsa	Vratsa	En recrutement

720 sites supplémentaires sont indiqués dans la fiche du registre.

Documents de l'étude

Aucun document n'est lié dans cette fiche du registre.

Évolution au fil du temps

Aucun changement n'a été enregistré depuis que nous avons intégré cette fiche pour la première fois.

Un changement est enregistré chaque fois que le promoteur met à jour la fiche du registre. Le statut, les dates, le recrutement et les sites apparaissent ici au fur et à mesure de leur évolution.

Registre: ClinicalTrials.gov · NCT########

https://xmedica.io/trials/ctgov/NCT04613596