A Study of Pembrolizumab Combination Therapy for Advanced Non-Small Cell Lung Cancer

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

19 Dec 2018 → 14 Jun 2025

Decision date (initial)

2024-04-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-500990-16-00

EudraCT number

2017-003134-85

WHO UTN

U1111-1278-8466

ClinicalTrials.gov

NCT03516981

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacodynamic, Pharmacogenomic, Diagnosis, Pharmacogenetic, Therapy, Safety

To evaluate the clinical activity (as assessed by objective response rate [ORR]) of specific pembrolizumab-based combinations.

Secondary objectives 2

1. To evaluate the clinical activity (as assessed by progression-free survival [PFS] and overall survival [OS]) of specific pembrolizumab-based combinations. PFS and OS to different specific pembrolizumab-based combinations will be assessed independently in each biomarker defined group
2. To determine the safety and tolerability of pembrolizumab in combination with MK-1308, MK-4280, or lenvatinib. Safety and tolerability to different specific pembrolizumab-based combinations will be assessed independently in each biomarker-defined group.

Conditions and MedDRA coding

Stage IV non-small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Has a histologically- or cytologically-confirmed diagnosis of Stage IV (American Joint Committee on Cancer [AJCC] v 8) NSCLC and has not had prior systemic therapy for advanced disease
2. Has confirmation that epidermal growth factor receptor- (EGFR-), anaplastic lymphoma kinase- (ALK-), c-ros oncogene 1- (ROS1-), or B isoform of rapidly accelerated fibrosarcoma- (B-Raf-) directed therapy is not indicated as primary therapy (documentation of absence of tumor activating EGFR mutations, B-Raf mutations, ALK gene rearrangements, and ROS1 gene rearrangements)
3. Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
4. Male participants must agree to use contraception during the treatment period and for ≥120 days, after the last dose of study treatment and refrain from donating sperm during this period. Male participants with pregnant partners must agree to use a condom
5. Female participants eligible to participate if not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees to follow contraceptive guidance during the treatment period and for ≥120 days after the last dose of study treatment
6. Provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
7. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
8. Has adequate organ function

Exclusion criteria 32

1. Has significant cardiovascular impairment within 12 months of the first dose of study drug: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability, significant cardiovascular impairment, or a left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram
2. Prolongation of QTc interval to >480 milliseconds (ms)
3. Has symptomatic ascites or pleural effusion
4. Has had an allogenic tissue/solid organ transplant
5. WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
6. Has not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy, or has had major surgery within 3 weeks prior to first dose of study intervention
7. Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula, gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
8. Radiographic evidence of major blood vessel invasion/infiltration
9. Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
10. Has received prior systemic chemotherapy treatment for metastatic/recurrent NSCLC
11. Has current NSCLC disease that can be treated with curative intent with surgical resection, localized radiotherapy, or chemoradiation
12. Is expected to require any other form of systemic or localized antineoplastic therapy while on study (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection)
13. Has received prior therapy with an anti–PD-1, anti–PD-L1, or anti–PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor
14. Has received previous treatment with another agent targeting the Lymphocyte-activation gene 3 (LAG-3) receptor
15. Has received previous treatment with another agent targeting vascular endothelial growth factor (VEGF) or the VEGF receptor
16. Has received prior anticancer therapy including investigational agents within 4 weeks prior to randomization
17. Has received prior radiotherapy within 2 weeks of start of study treatment or received lung radiation therapy of >30 Gy within 6 months prior to the first dose of study intervention
18. Has received a live or live-attenuated vaccine within 30 days before the first dose of study treatment
19. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
20. 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 the first dose of study treatment
21. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
22. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
23. Has severe hypersensitivity (≥Grade 3) to pembrolizumab, favezelimab, or lenvatinib and/or any of its excipients
24. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
25. Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
26. Has an active infection requiring systemic therapy
27. Has a known history of human immunodeficiency virus (HIV) infection
28. Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
29. Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
30. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
31. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
32. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days (females and males) after the last dose of study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

Secondary endpoints 4

1. Progression Free Survival (PFS) per RECIST 1.1
2. Overall Survival (OS)
3. Number of Participants Experiencing Adverse Events (AEs)
4. Number of Participants Discontinuing Study Drug Due to AEs

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Jianda Yuan

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Jianda Yuan

Third parties 4

Locations

3 EU/EEA countries · 9 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 30 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