Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Plus Chemotherapy in Participants With Metastatic Esophageal Carcinoma (MK-7902-014/E7080-G000-320/LEAP-014)

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

21 Jul 2021 → 20 May 2026

Decision date (initial)

2023-08-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-501342-29-00

EudraCT number

2020-001911-26

WHO UTN

U1111-1280-1020

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Pharmacokinetic

1. Part 1 (FP and TP Safety Run-in): To evaluate the safety and tolerability of treatment with lenvatinib + pembrolizumab in combination with FP or TP.
2. Part 2 (Main Study): To compare OS between treatment arms.

Secondary objectives 5

1. Part 2 (Main Study): To compare PFS per RECIST 1.1, as determined by blinded independent central review (BICR), between treatment arms
2. Part 2 (Main Study): To compare ORR per RECIST 1.1, as determined by BICR, between treatment arms.
3. Part 2 (Main Study): To evaluate DOR per RECIST 1.1, as determined by BICR, between treatment arms
4. Part 2 (Main Study): To compare OS and PFS, ORR, DOR, per RECIST 1.1 assessed by BICR between treatment arms in participants whose tumors are PD-L1 CPS ≥10.
5. Part 2 (Main Study): To evaluate the safety and tolerability profile of lenvatinib + pembrolizumab in combination with chemotherapy versus permbrolizumab + chemotherapy

Conditions and MedDRA coding

Esophageal Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Has a histologically or cytologically confirmed diagnosis of metastatic squamous cell carcinoma of the esophagus
2. Male participants are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of lenvatinib or 90 days after the last dose of chemotherapy, whichever comes last; 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only and is greater than 90 days post chemotherapy, no male contraception is needed
3. Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP using a contraceptive method that is highly effective or is abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 120 days after the last dose of pembrolizumab, 30 days after the last dose of lenvatinib, or 180 days after the last dose of chemotherapy, whichever occurs last, and agrees not to donate eggs during this period
4. Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP≤150/90 millimeters of mercury (mm Hg) with no change in antihypertensive medications within 1 week prior to randomization
5. Has adequate organ function

Exclusion criteria 23

1. Has had previous therapy for locally advanced unresectable or metastatic esophageal cancer
2. Has locally advanced esophageal carcinoma
3. Has metastatic adenocarcinoma of the esophagus
4. Has direct invasion into adjacent organs such as the aorta or trachea
5. Has radiographic evidence of encasement of a major blood vessel, or of intratumoral cavitation
6. Has perforation risks or significant gastrointestinal (GI) bleeding
7. Has had clinically significant hemoptysis within 3 weeks prior to the first dose of study drug or tumor bleeding within 2 weeks prior to the first dose of study intervention
8. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention
9. Has GI obstruction, poor oral intake, difficulty in taking oral medication, or existing esophageal stent
10. Has had major surgery, open biopsy, or significant traumatic injury within 3 weeks prior to first dose of study interventions
11. Has received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis
12. Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention; administration of killed vaccines is allowed
13. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention, or has a history of organ transplant, including allogeneic stem cell transplant
14. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
15. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
16. Has an active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed
17. Has a history of non-infectious pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
18. Has poorly controlled diarrhea
19. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
20. Has peripheral neuropathy ≥Grade 2
21. Has a known history of human immunodeficiency virus (HIV) infection
22. Has a known history of Hepatitis B or known active Hepatitis C virus infection
23. Has a weight loss of >20% within the last 3 months

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1 (5-Fluorouracil [5-FU] plus cisplatin [FP] and paclitaxel plus cisplatin [TP] Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs)
2. Part 1 (FP and TP Safety Run-in): Number of Participants With Adverse Events (AEs)
3. Part 1 (FP and TP Safety Run-in): Number of Participants who Discontinued Study Treatment Due to an AE
4. Part 2 (Main Study): Overall Survival (OS) in all Participants

Secondary endpoints 9

1. Part 2 (Main Study): 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 all Participants
2. Part 2 (Main Study): Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR in all Participants
3. Part 2 (Main Study): Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR in all Participants
4. Part 2 (Main Study): OS in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10
5. Part 2 (Main Study): PFS per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10
6. Part 2 (Main Study): ORR per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10
7. Part 2 (Main Study): DOR per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10
8. Part 2 (Main Study): Number of Participants With AEs
9. Part 2 (Main Study): Number of Participants who Discontinued Study Treatment Due to an AE

Investigational products

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

Test 9

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

Sucharita Bhaumik

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Sucharita Bhaumik

Third parties 4

Locations

6 EU/EEA countries · 36 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 57 files

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

Application history

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