A clinical study of pembrolizumab and other treatments for non-small cell lung cancer (MK-3475-01G)

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

18 Apr 2025 → ongoing

Decision date (initial)

2025-04-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2024-515772-12-00

WHO UTN

U1111-1309-7532

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

1. To evaluate ORR per RECIST 1.1 as assessed by BICR
2. To evaluate the safety and tolerability of investigational treatment combinations based on proportion of AEs

Secondary objectives 3

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

Conditions and MedDRA coding

Lung neoplasm malignant (Stage IV Non-small cell lung cancer)

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Histologically or cytologically confirmed diagnosis of Stage IV squamous or non-squamous non-small cell lung cancer (NSCLC) per American Joint Committee on Cancer (AJCC) Staging Manual Version 8
2. Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1 as assessed within 7 days before randomization
3. Has archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided
4. Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on ART
5. Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to treatment randomization

Exclusion criteria 31

1. Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
2. Participants with squamous histology are excluded if there is a known tumor-activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) or c ros oncogene 1 (ROS1) gene rearrangement
3. Is HIV-infected with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
4. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement
5. Has evidence of any leptomeningeal disease
6. Has known history of, or active, neurologic paraneoplastic syndrome
7. Has clinically significant corneal disease
8. Has myocardial infarction within 6 months
9. Has New York Heart Association (NYHA) Classes 3 or 4 congestive heart failure
10. Has uncontrolled angina pectoris within 6 months
11. Has cardiac arrhythmia requiring ongoing antiarrhythmic treatment
12. Has history of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes
13. Has bradycardia of less than 50 beats per minute (bpm) unless the participant has a pacemaker
14. Has history of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers, and have no history of fainting or clinically relevant arrhythmia with pacemakers
15. Has coronary/peripheral artery bypass graft within 6 months
16. Has complete left bundle branch block
17. Has inadequate washout period from prior concomitant therapy as specified in protocol before randomization
18. Has received prior treatment with a topoisomerase I inhibitor or an anti-HER3 antibody and/or ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor
19. Has received prior systemic anticancer therapy for their metastatic NSCLC
20. Has received prior therapy with an anti- programmed cell death 1 protein (anti-PD-1), anti- programmed cell death ligand 1 protein (anti-PD-L1), or anti- programmed cell death ligand 2 protein (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor
21. Has received prior radiotherapy within 2 weeks of randomization, has radiation related toxicity requiring corticosteroids, or has had radiation pneumonitis
22. Has Received radiation therapy to the lung that is >30 gray within 6 months of start of study intervention
23. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
24. Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
25. Has known additional malignancy that is progressing or has required active treatment within the past 3 years
26. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
27. Has severe hypersensitivity to any of the study interventions and/or any of their excipients
28. Has active autoimmune disease that has required systemic treatment in the past 2 years
29. Has active infection requiring systemic therapy
30. Has concurrent active Hepatitis B and Hepatitis C virus infection
31. Have not adequately recovered from major surgery or have ongoing surgical complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Objective Response Rate (ORR)
2. Number of Participants Who Experience an Adverse Event (AE)
3. Number of Participants Who Discontinue Study Treatment Due to an AE

Secondary endpoints 3

1. Duration of Response (DOR)
2. Progression-Free Survival (PFS)
3. Overall Survival (OS)

Investigational products

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

Test 2

Comparator 4

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

Azadeh Namakydoust

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Azadeh Namakydoust

Third parties 7

Locations

5 EU/EEA countries · 15 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 44 files

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

Application history

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