CTRI

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CTRI Number

CTRI/2026/01/100675 [Registered on: 09/01/2026] Trial Registered Prospectively

Last Modified On:

06/01/2026

Post Graduate Thesis

Type of Trial

Interventional

Type of Study

Drug

Study Design

Randomized, Parallel Group, Placebo Controlled Trial

Public Title of Study

A clinical trial involving a new drug combination for treatment of advanced lung cancer with KRAS G12C mutation

Scientific Title of Study

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 KRASG12C Mutation.

Trial Acronym

KRYSTAL-4

Secondary IDs if Any

Secondary ID	Identifier
2024-515698-85	EudraCT
CA239-0004 dated 25-Sep-2024	Protocol Number

Details of Principal Investigator or overall Trial Coordinator (multi-center study)

Name	Shilpi Sinha
Designation	Director, Country Head RCO India
Affiliation	Bristol-Myers Squibb India Pvt. Ltd.
Address	Bristol-Myers Squibb India Pvt. Ltd. One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphistone (W), Mumbai- 400013 India Mumbai MAHARASHTRA 400013 India
Phone	02266288600
Fax
Email	shilpi.sinha@bms.com

Details of Contact Person
Scientific Query

Name	Dr Kartik Doshi
Designation	Associate Director, Medical India
Affiliation	Bristol Myers Squibb India Pvt. Ltd.
Address	Bristol-Myers Squibb India Pvt. Ltd. One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphistone (W), Mumbai- 400013 India Mumbai MAHARASHTRA 400013 India
Phone	02266288600
Fax
Email	kartik.doshi@bms.com

Details of Contact Person
Public Query

Name	Shilpi Sinha
Designation	Director, Country Head RCO India
Affiliation	Bristol-Myers Squibb India Pvt. Ltd.
Address	Bristol-Myers Squibb India Pvt. Ltd. One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphistone (W), Mumbai- 400013 India Mumbai MAHARASHTRA 400013 India
Phone	02266288600
Fax
Email	shilpi.sinha@bms.com

Source of Monetary or Material Support

BRISTOL MYERS SQUIBB INDIA PRIVATE LIMITED One International Center, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai- 400013 India

Primary Sponsor

Name	Mirati Therapeutics Inc, a Bristol Myers Squibb Company
Address	Route 206 & Province Line Road Princeton, NJ 08543
Type of Sponsor	Pharmaceutical industry-Global

Details of Secondary Sponsor

Name	Address
NIL	NIL

Countries of Recruitment

Argentina
Australia
Belgium
Brazil
Bulgaria
Chile
China
Colombia
Croatia
France
Germany
Greece
Hong Kong
Hungary
India
Ireland
Israel
Italy
Japan
Mexico
Netherlands
Poland
Portugal
Republic of Korea
Romania
Saudi Arabia
Spain
Switzerland
Taiwan
Thailand
Turkey
United Kingdom
United States of America

Sites of Study

Details of Ethics Committee

No of Ethics Committees= 15
Name of Committee	Approval Status
Ethics Committee N.S.C.B.C Research Institute	Approved
Ethics Committee of Marengo Asia Healthcare Pvt Ltd	Approved
Human Ethics committee	Submittted/Under Review
Institutional Ethics Committee	Approved
Institutional Ethics Committee	Approved
Institutional Ethics Committee	Submittted/Under Review
Institutional Ethics Committee VMMC & SJH	Submittted/Under Review
Institutional Ethics committee(I/III)	Submittted/Under Review
Institutional Ethics Committee,MPMMCC AND HBCH	Submittted/Under Review
Institutional Ethics Committee-Clinical studies	Approved
Institutional Ethics CommitteeYashoda Academy of Medical Education & Research	Approved
Institutional Ethics Committtee	Approved
Institutional review Board	Approved
NHS Ethics Committee	Approved
Swarnim Ethics Committee	Approved

Regulatory Clearance Status from DCGI

Status

Approved/Obtained

Health Condition / Problems Studied

Health Type	Condition
Patients	, (1) ICD-10 Condition: C349\|\|Malignant neoplasm of unspecifiedpart of bronchus or lung,

Intervention / Comparator Agent

Type	Name	Details
Intervention	Arm A: Adagrasib + Pembrolizumab + Pemetrexed + Cisplatin/Carboplatin	Approximately 16 cycles treatment (each cycle is of 3 weeks). Following drug will be administered: i) Adagrasib 400 mg BID - Oral ii) Pembrolizumab on Day 1 of each 21 day cycle for a maximum 24 months - Intravenous infusion iii) Pemetrexed 500mg/m2 every 3 weeks - Intravenous iv) Carboplatin AUC 5mg/ml/min every 3 weeks - Intravenous OR Cisplatin 75mg/m2 every 3 weeks - Intravenous
Comparator Agent	Arm B: Placebo + Pembrolizumab + Pemetrexed + Cisplatin/Carboplatin	Approximately 16 cycles treatment (each cycle is of 3 weeks). Following drug will be administered: i) Placebo 400 mg BID - Oral ii) Pembrolizumab on Day 1 of each 21 day cycle for a maximum 24 months - Intravenous infusion iii) Pemetrexed 500mg/m2 every 3 weeks - Intravenous iv) Carboplatin AUC 5mg/ml/min every 3 weeks - Intravenous OR Cisplatin 75mg/m2 every 3 weeks - Intravenous

Inclusion Criteria

Age From	18.00 Year(s)
Age To	99.00 Year(s)
Gender	Both
Details	1. Histologically or cytologically confirmed diagnosis of non-squamous NSCLC 2. Locally advanced or metastatic disease 3. Measurable disease via computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria of at least 1 lesion 4. No prior systemic anti-cancer therapy given for advanced or metastatic disease 5. Not a candidate for definitive therapy (eg chemoradiation or complete surgical resection) 6. Evidence of KRAS G12C mutation via tumor tissue and or ctDNA documented by Sponsor-approved laboratory testing 7. Any PD L1 expression (0 to 100 percentage ) as determined by VENTANA PD-L1 (SP263) assay, Agilent PD-L1 IHC 22C3 pharmDx or Agilent PD-L1 IHC 28-8 pharmDx. If despite best efforts a quantifiable result is not possible non-evaluable or non-quantifiable results may be acceptable upon Medical Monitor (or designee) approval for a maximum of 10 percentage of total participants. 8. 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 less than or equal to 20 mm in diameter.

ExclusionCriteria

Details

1.Participants with an active known prior documented or suspected autoimmune or inflammatory disease
2.Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment
3.Inadequate bone marrow function
4.Inadequate liver function
5.Ongoing treatment with concomitant medication known to cause prolonged QTc interval and that cannot be switched to alternative treatment prior to study entry
6.Treatment targeting KRAS G12C mutation (eg sotorasib adagrasib) in any setting
7.Certain significant ECG abnormalities
8.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug

Method of Generating Random Sequence

Computer generated randomization

Method of Concealment

Centralized

Blinding/Masking

Participant and Investigator Blinded

Primary Outcome

Outcome	TimePoints
Progression free survival per RECIST v1.1 according to Blinded Independent Central Review (BICR)	1) Body scans Q6W until 1.5 years, then Q12W until BICR-confirmed progressive disease, even if the participant has discontinued study treatment. 2) Brain imaging Q6W (if baseline brain metastases) or Q12W (if no baseline brain metastases) until 1.5 years, then Q12W.

Secondary Outcome

Outcome	TimePoints
1) Overall Response & Duration of Response per RECIST v1.1 according to BICR & progression free survival according to investigator. 2) Treatment-related & all-cause AEs/SAEs, AEs leading to dose modifications, & fatal AEs 3) Patient related outcome assessments: NSCLC-SAQ & EORTC QLQ-C30	1) Patient survival follow up to 7 years, Death, withdrawal of consent, loss to follow up or End of study whichever occurs first 2) Until disease progression or participants who discontinue treatment due to reasons other than disease progression.

Target Sample Size

Total Sample Size="630"
Sample Size from India="29"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"

Phase of Trial

Phase 3

Date of First Enrollment (India)

01/03/2026

Date of Study Completion (India)

Applicable only for Completed/Terminated trials

Date of First Enrollment (Global)

30/04/2025

Date of Study Completion (Global)

Applicable only for Completed/Terminated trials

Estimated Duration of Trial

Years="7"
Months="0"
Days="0"

Recruitment Status of Trial (Global)

Open to Recruitment

Recruitment Status of Trial (India)

Not Yet Recruiting

Publication Details

N/A

Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?

Response - NO

Brief Summary

This study is a randomized, double-blind, placebo-controlled, Phase 3 clinical trial evaluating

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. Treatment will continue until confirmed PD, death, unacceptable toxicity, or withdrawal of consent.

All participants will have an End of Treatment (EOT) visit to collect safety and efficacy assessments. Once the participant

completes the end of treatment visit, they will enter the follow up period.