Recruiting NCT06875310

A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

Phase III Interventional Carcinoma, Non-Small-Cell Lung

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Adagrasib, Pembrolizumab, Carboplatin, Pemetrexed.
Who it may be relevant to: Registry conditions: Carcinoma, Non-Small-Cell Lung. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Austria, Belgium +30
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

A Randomized, Double-Blind, Phase 3 Trial of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated, Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

Overview

This is a trial to evaluate the efficacy, safety, and tolerability of adagrasib plus pembrolizumab plus platinum-doublet chemotherapy versus placebo plus pembrolizumab plus platinum-doublet chemotherapy in participants with previously untreated, locally advanced or metastatic NSCLC with KRAS G12C mutation

Interventions

Drug Adagrasib
Specified dose on specified days
Drug Pembrolizumab
Specified dose on specified days
Drug Carboplatin
Specified dose on specified days
Drug Pemetrexed
Specified dose on specified days
Drug Placebo
Specified dose on specified days
Drug Cisplatin
Specified dose on specified days

Primary outcome measures

Progression Free Survival (PFS) as Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Blinded Independent Central Review (BICR) [Time frame: Up to 7 years]
Overall Survival (OS) [Time frame: Up to 7 years]

Secondary outcome measures (11)

Overall Response (OR) as Assessed per RECIST v1.1 by BICR [Time frame: Up to 7 years]
Duration of Response (DOR) as Assessed per RECIST 1.1 by BICR [Time frame: Up to 7 years]
PFS as Assessed per RECIST v1.1 by Investigator [Time frame: Up to 7 years]
Number of Participants With Adverse Events (AEs) [Time frame: Up to 90 days from last dose]
Number of Participants With Serious Adverse Events (SAEs) [Time frame: Up to 90 days from last dose]
Number of Participants With AEs Leading to Dose Interruption [Time frame: Up to 90 days from last dose]
Number of Participants With AEs Leading to Dose Reduction [Time frame: Up to 90 days from last dose]
Number of Participants With AEs Leading to Treatment Discontinuation [Time frame: Up to 90 days from last dose]
Number of Deaths [Time frame: Up to 90 days from last dose]
Time to Definitive Deterioration by Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score [Time frame: Up to 7 years]
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) Scale/item Score [Time frame: Up to 90 days from last dose]

Eligibility criteria

Inclusion criteria

Histologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor sample and/or circulating tumor deoxyribonucleic acid (ctDNA).
Locally advanced or metastatic disease.
Measurable disease via computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria of at least 1 lesion.
No prior systemic anti-cancer therapy given for advanced or metastatic disease.
Not a candidate for definitive therapy (eg, chemoradiation or complete surgical resection).
Participants with brain metastases are eligible for enrollment, including those with untreated brain metastases. Brain metastases must be asymptomatic and not in need of immediate local therapy. Any untreated brain metastases must be ≤ 20 mm in diameter.
Any PD-L1 expression (0 to 100%) as determined by VENTANA PD-L1 (SP263) assay, Agilent PD-L1 IHC 22C3 pharmDx, or Agilent PD-L1 IHC 28-8 pharmDx.

Exclusion criteria

Participants with an active autoimmune or inflammatory disease requiring systemic treatment within 2 years.
Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment that are ongoing or with risk of recurrence.
Inadequate bone marrow or liver function or electrocardiogram (ECG) abnormalities.
Ongoing treatment with concomitant medication known to cause prolonged QTc interval and that cannot be switched to alternative treatment prior to study entry.
Treatment targeting KRAS G12C mutation (eg, sotorasib, adagrasib) in any setting.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration.
Other protocol-defined Inclusion/Exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Quadruple blind
Primary purpose: Treatment