Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) Plus Chemotherapy in Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-7902-015/E7080-G000-321/LEAP-015) (LEAP-015)

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

24 Feb 2021 → 30 Mar 2026

Decision date (initial)

2024-01-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-504834-23-00

EudraCT number

2020-001990-53

WHO UTN

U1111-1288-1010

ClinicalTrials.gov

NCT04662710

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

1. Objective (Part 1): To evaluate the safety and tolerability of treatment with lenvatinib plus pembrolizumab plus chemotherapy.
2. Objective (Part 2): To compare the overall survival between treatment groups.
3. Objective (Part 2): To compare the PFS between treatment groups.

Secondary objectives 3

1. Objective (Part 2): To compare ORR between treatment groups.
2. Objective (Part 2): To estimate DOR, per RECIST 1.1 as assessed by BICR for each treatment group in participants with programmed cell death ligand 1 combined positive score ≥1 and in all participants.
3. Objective (Part 2): To evaluate the safety and tolerability of lenvatinib plus pembrolizumab plus chemotherapy versus chemotherapy.

Conditions and MedDRA coding

Advanced/Metastatic Gastroesophageal Adenocarcinoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Has histologically and/or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic gastroesophageal adenocarcinoma
2. Is not expected to require tumor resection during the treatment course
3. Has gastroesophageal adenocarcinoma that is not HER-2/neu positive
4. Has measurable disease as by RECIST 1.1 by scan with IV contrast as determined by the local site investigator
5. Male participants agree to refrain from donating sperm and agree to either remain abstinent from heterosexual intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for >7 days after last dose of lenvatinib or 90 days after last dose of chemotherapy-whichever comes last
6. Female participants not pregnant or breastfeeding are eligible to participate if not a women of childbearing potential (WOCBP), or if a WOCBP they either use a contraceptive method that is highly effective OR remain abstinent from heterosexual intercourse as their preferred and usual lifestyle, and do not donate eggs (ova,oocytes) to others or freeze/store for their own use, and abstain from breastfeeding during the intervention period through 120 days after last dose of pembrolizumab, 30 days after last dose of lenvatinib, or 180 days after last dose of chemotherapy-whichever occurs last
7. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of study treatment
8. Has adequately controlled blood pressure with or without antihypertensive medications
9. Has adequate organ function

Exclusion criteria 22

1. Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ) esophageal adenocarcinoma
2. Has had major surgery within 28 days prior to first dose of study interventions
3. Has had radiotherapy within 14 days of randomization
4. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
5. Has known CNS metastases and/or carcinomatous meningitis
6. Has severe hypersensitivity (>Grade 3) to treatment with an monoclonal antibody (mAb) or known sensitivity or intolerance to any component of lenvatinib, pembrolizumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum containing products
7. Has had an allogeneic tissue/solid organ transplant
8. Has perforation risks or significant gastrointestinal (GI) bleeding
9. Has GI obstruction, poor oral intake (CAPOX participants), or difficulty in taking oral medication (CAPOX participants)
10. 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 coinhibitory T-cell receptor
11. Has received prior therapy with anti-vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor or anti-VEGF mAb
12. Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug
13. 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)
14. Has radiographic evidence or encasement or invasion of a major blood vessel, or of intertumoral cavitation
15. Has inadequate cardiac function
16. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
17. Has poorly controlled diarrhea
18. Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
19. Has peripheral neuropathy >Grade 2
20. Has a known history of human immunodeficiency virus (HIV) or HIV 1/2 antibodies
21. Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
22. Has weight loss of >20% within the last 3 months

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
2. Part 1: Number of Participants with Adverse Events (AEs)
3. Part 1: Number of Participants who Discontinued Study Treatment Due to an AE
4. Part 2: Overall Survival (OS) in Participants with Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
5. Part 2: OS in All Participants
6. Part 2: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants with PD-L1 CPS ≥1
7. Part 2: PFS Per RECIST 1.1 as Assessed by BICR in All Participants

Secondary endpoints 6

1. Part 2: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS ≥1
2. Part 2: ORR Per RECIST 1.1 as Assessed by BICR in All Participants
3. Part 2: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS ≥1
4. Part 2: DOR Per RECIST 1.1 as Assessed by BICR in All Participants
5. Part 2: Number of Participants with AEs
6. Part 2: Number of Participants who Discontinued Study Treatment Due to an AE

Investigational products

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

Test 12

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

Sonal Bordia

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Sonal Bordia

Third parties 8

Locations

7 EU/EEA countries · 39 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 79 files

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

Application history

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