Phase 2 First-Line ES-SCLC Platform Study

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

12 Aug 2021 → 23 Jun 2025

Decision date (initial)

2024-02-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-506538-56-00

EudraCT number

2020-005649-17

WHO UTN

U1111-1293-9965

ClinicalTrials.gov

NCT04924101

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacodynamic, Efficacy, Pharmacokinetic

1. To estimate the objective response rate as assessed by blinded independent central review according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
2. To estimate 6-month progression free survival rate as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1

Secondary objectives 6

1. To evaluate duration of response based on RECIST 1.1 as assessed by blinded independent central review
2. To evaluate progression free survival based on RECIST 1.1 as assessed by blinded independent central review
3. To evaluate overall survival
4. To evaluate the best tumor size change as assessed by blinded independent central review
5. To evaluate the safety and tolerability of investigational treatment combinations based on proportion of adverse events
6. To evaluate changes in health-related quality of life assessments from baseline using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30)

Conditions and MedDRA coding

First-line treatment of participants with extensive-stage small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Has histologically or cytologically confirmed diagnosis of extensive-stage small cell lung cancer (ES-SCLC) in need of first-line therapy
2. Has ES-SCLC defined as Stage IV (T any, N any, M1a/b/c) by the American Joint Committee on Cancer, Eighth Edition
3. Male participants are eligible to participate if they agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: Lenvatinib (7 days); Etoposide, Cisplatin, or Carboplatin (180 days) and Pembrolizumab, MK-4830, or (no contraception measures); refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent or must agree to use contraception per protocol unless confirmed to be azoospermic
4. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman/women of childbearing potential (WOCBP) or is a WOCBP and uses a contraceptive method that is highly effective with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: Lenvatinib (30 days), Etoposide, Cisplatin, or Carboplatin (180 days), and Pembrolizumab, MK-4830, or Boserolimab (120 days)
5. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours (urine test) or 72 hours (serum test) before the first dose of study intervention
6. Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention
7. Has measurable disease per RECIST 1.1 as assessed by local site investigator/radiology and verified by blinded independent central review (BICR)
8. Submits an archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated where such sample exist
9. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days before randomization
10. Has adequate organ function within 10 days before the first dose of study intervention
11. Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no changes in antihypertensive medications within 1 week before randomization

Exclusion criteria 32

1. Has had major surgery within 3 weeks before first dose of study interventions
2. Has a preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
3. Has urine protein ≥1 g/24 hours
4. Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multiple gated acquisition (MUGA) or echocardiogram (ECHO)
5. Prolongation of QT interval with Fridericia's correction (QTcF) interval to >480 ms
6. Has clinically significant cardiovascular disease or major arterial thromboembolic event within 12 months before first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
7. Has active hemoptysis within 3 weeks before the first dose of study intervention
8. Has gastrointestinal malabsorption or any other condition that might affect oral study intervention absorption
9. Has serious nonhealing wound, ulcer, or bone fracture within 28 days before first dose of study intervention
10. Has any major hemorrhage or venous thromboembolic events within 3 months before the first dose of study intervention. Participants with venous thrombosis diagnosed more than 3 months before the first dose of study intervention must be on stable doses of anticoagulants
11. Has a history of inflammatory bowel disease
12. Has a history of a gastrointestinal perforation within 6 months before the first dose of study intervention
13. Is considered a poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease
14. Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
15. Has received prior treatment (chemotherapy, radiotherapy, or surgical resection) including investigational agents for SCLC
16. Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy, while on study
17. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
18. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
19. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. A participant that meets this exclusion criterion but is otherwise deemed eligible for the study may be randomized across the specific intervention groups
20. Has symptomatic ascites, pleural effusion, or pericardial effusion. A participant who is clinically stable following treatment for these conditions is eligible
21. 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 intervention
22. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
23. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with brain metastases may participate only if they satisfy all of the following: a) Completed treatment at least 14 days before the first dose of study intervention b) Have no evidence of new or enlarging brain metastases confirmed by posttreatment repeat brain imaging performed at least 4 weeks after pretreatment brain imaging, and c) Are neurologically stable without the need for steroids for at least 7 days before the first dose of study intervention as per local site assessment. Participants with untreated brain metastases will be allowed if they are asymptomatic, the investigator determines there is no immediate CNS-specific treatment required, there is no significant surrounding edema, and the brain metastases are of 5 mm or less in size and 3 or fewer in number
24. Has a history of severe hypersensitivity reaction to any study intervention and/or any of its excipients
25. Has an active autoimmune disease that has required systemic treatment in past 2 years
26. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
27. Has a known history of, or active, neurologic paraneoplastic syndrome
28. Has an active infection requiring systemic therapy
29. Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B virus infection or an active Hepatitis C infection
30. Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
31. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study
32. Has had an allogenic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
2. Six-Month Progression-Free Survival (PFS) as Assessed by BICR per RECIST 1.1

Secondary endpoints 7

1. Duration of Response (DOR) as Assessed by BICR per RECIST 1.1
2. PFS as Assessed by BICR per RECIST 1.1
3. Overall Survival (OS)
4. Percent Change From Baseline in Tumor Size as Assessed by BICR
5. Number of Participants Who Experienced an Adverse Event (AE)
6. Number of Participants Who Discontinued Study Treatment Due to an AE
7. Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Global Health Status/Quality of Life Scale (Items 29 and 30) at Week 19

Investigational products

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

Test 6

Auxiliary 3

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

Humberto Lara-Guerra

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Humberto Lara-Guerra

Third parties 8

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 37 files

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

Application history

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