A clinical study of new treatments for non-small cell lung cancer (MK-3475-01J)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Mar 2026 → ongoing

Decision date (initial)

2026-02-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2025-521939-36-00

WHO UTN

U1111-1321-3999

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Safety, Efficacy, Pharmacokinetic

1. To evaluate the safety and tolerability of investigational agent combinations
2. To evaluate ORR per RECIST 1.1 as assessed by BICR

Secondary objectives 4

1. To evaluate DOR per RECIST 1.1 as assessed by BICR
2. To evaluate PFS per RECIST 1.1 as assessed by BICR
3. To evaluate OS
4. To characterize the PK of investigational agent combinations

Conditions and MedDRA coding

Participants with KRAS G12C-Mutant, Advanced or Metastatic Nonsquamous NSCLC

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Has histologically or cytologically confirmed diagnosis of advanced or metastatic nonsquamous Non-Small Cell Lung Cancer (NSCLC)
2. Has tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA) that demonstrates the presence of Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutations
3. Can provide an archival tumor tissue sample or newly obtained core, incisional, excisional biopsy of a tumor lesion not previously irradiated
4. Has recovered to ≤Grade 1 or baseline from any Adverse events (AEs) due to previous anticancer therapies and/or ≤Grade 2 neuropathy and/or endocrine-related AEs adequately treated with hormone replacement
5. Has well controlled human immunodeficiency virus (HIV) on antiretroviral therapy (ART) if HIV-infected
6. Has undetectable hepatitis B (HBV) viral load and have received HBV antiviral therapy for at least 4 weeks if hepatitis B surface antigen (HBsAg) positive
7. Has undetectable hepatitis C (HCV) viral load if HCV-infected

Exclusion criteria 16

1. Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
2. Has HIV-infection with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
3. Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
4. Has uncontrolled, clinically significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of corrected QT interval corrected for heart rate by Fridericia's formula (QTcF) interval to >470 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention
5. Has received prior systemic anticancer therapy for advanced or metastatic NSCLC
6. Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE) (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis
7. Has received previous treatment with an agent targeting KRAS
8. Has received prior systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) and has not recovered to grade ≤ 1 or baseline from AE associated with anticancer therapy before allocation/randomization
9. Has received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
11. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
12. Has a known active central nervous system (CNS) metastases and/or carcinomatous meningitis
13. Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
14. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
15. Has a history of stem cell/solid organ transplant
16. Has not adequately recovered from major surgery or has ongoing surgical complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Percentage of Participants with a Dose Limiting Toxicity (DLT)
2. Percentage of Participants who Experience at Least One Adverse Event (AE)
3. Percentage of Participants who Discontinue Study Intervention Due to an AE
4. Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by Blinded Independent Central Review (BICR)

Secondary endpoints 6

1. Duration of Response (DOR) per RECIST 1.1 as assessed by BICR
2. Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR
3. Overall Survival (OS)
4. Area Under the Concentration-Time Curve (AUC) for MK-1084
5. Maximum Concentration (Cmax) of MK-1084
6. Trough Concentration (Ctrough) of MK-1084

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Atsuko Ogino

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Atsuko Ogino

Third parties 6

Locations

5 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications