Study of Combination Therapies in Esophageal Cancer

Start 28 Mar 2023 · Status Ongoing, recruiting · 3 EU/EEA countries · 8 sites · Protocol MK-3475-06B

Overview

Sponsor-declared trial summary

Phase Phase I and Phase II (Integrated) - Other

Status Ongoing, recruiting

Participants planned 78

Countries 3

Sites 8

Advanced esophageal squamous cell carcinoma

1. Safety Lead-In Phase: To evaluate the safety and tolerability of combination treatments that have not been evaluated in a separate study. 2. To estimate the 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)…

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: 28 Mar 2023 → ongoing
Decision date (initial): 2024-07-01
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: Merck Sharp & Dohme LLC

External identifiers

EU CT number: 2023-505189-26-00
EudraCT number: 2021-005443-76
WHO UTN: U1111-1291-1987
ClinicalTrials.gov: NCT05319730

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy, Efficacy

1. Safety Lead-In Phase: To evaluate the safety and tolerability of combination treatments that have not been evaluated in a separate study.
2. To estimate the 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).

Secondary objectives 4

Efficacy Phase: To evaluate progression-free survival (PFS) as assessed by BICR per RECIST 1.1.
Efficacy Phase: To evaluate the duration of response (DOR) as assessed by BICR per RECIST 1.1.
Efficacy Phase: To evaluate overall survival (OS).
Efficacy Phase: To evaluate the safety and tolerability of investigational treatment arms based on the proportion of participants with AEs.

Conditions and MedDRA coding

Advanced esophageal squamous cell carcinoma

Version	Level	Code	Term	System organ class
25.1	LLT	10030186	Oesophageal squamous cell carcinoma NOS	10029104

Regulatory references

Plan to share IPD: Yes

EU CT number	Title	Sponsor
2023-504918-29-00	An Open-label, Randomized Phase 3 Study of MK-2870 as a Single Agent and in Combination with Pembrolizumab Versus Treatment of Physician’s Choice in Participants with HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer	Merck Sharp & Dohme LLC
2023-508323-12-00	A Phase 3 Randomized, Active-controlled, Open-label, Multicenter Study to Compare the Efficacy and Safety of MK-2870 Monotherapy Versus Treatment of Physician’s Choice as Second-line Treatment for Participants with Recurrent or Metastatic Cervical Cancer (TroFuse-020/GOG-3101/ENGOT-cx20)	Merck Sharp & Dohme LLC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable esophageal squamous cell carcinoma (ESCC).
Has experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy, that includes a platinum agent and previous exposure to an anti-programmed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1) based immuneoncology (IO) therapy.
Has provided an archival or most recent tumor tissue sample obtained as part of clinical practice.
Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.

Exclusion criteria 11

Direct invasion into adjacent organs such as the aorta or trachea.
Has experienced weight loss >10% over approximately 2 months prior to first dose of study therapy.
Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease.
Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has undergone potentially curative therapy.
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Participants with human immunodeficiency virus (HIV) with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease.
History of allogenic tissue/solid organ transplant.
Clinically significant cardiovascular disease within 12 months from first dose of study intervention.
Has risk for significant GI bleeding such as a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization, significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

Number of Participants Experiencing Dose-limiting Toxicities (DLTs) During Safety Lead-in Phase
Number of Participants Who Experienced an Adverse Event (AE) During Safety Lead-in Phase
Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase
Objective Response Rate (ORR)

Secondary endpoints 5

Progression-Free Survival (PFS)
Duration of Response (DOR)
Overall Survival (OS)
Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase
Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase

Investigational products

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

Test 8

KEYTRUDA 25 mg/mL concentrate for solution for infusion

PRD4323105 · Product

Active substance: Pembrolizumab
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS USE
Authorisation status: Authorised
ATC code: L01FF02 — -
Marketing authorisation: EU/1/15/1024/002
MA holder: MERCK SHARP & DOHME B.V.
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Irinotecan Hydrochloride

SCP105621456 · ATC

Active substance: Irinotecan Hydrochloride
Route of administration: INTRAVENOUS USE
Authorisation status: Authorised
ATC code: L01CE02 — IRINOTECAN
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Lenvatinib

PRD9414230 · Product

Active substance: Lenvatinib
Pharmaceutical form: CAPSULE
Route of administration: ORAL
Authorisation status: Not Authorised
MA holder: MERCK & CO. INC.
Paediatric formulation: No
Orphan designation: No

Lenvatinib

PRD9414231 · Product

Active substance: Lenvatinib
Pharmaceutical form: CAPSULE
Route of administration: ORAL
Authorisation status: Not Authorised
MA holder: MERCK & CO. INC.
Paediatric formulation: No
Orphan designation: No

Paclitaxel

SCP129816 · ATC

Active substance: Paclitaxel
Substance synonyms: ONCOGEL, ABI-007, MBT 0206
Route of administration: INTRAVENOUS USE
Authorisation status: Authorised
ATC code: L01CD01 — PACLITAXEL
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

MK-2870

PRD11447874 · Product

Active substance: Sacituzumab Tirumotecan
Substance synonyms: Humanised IgG1 monoclonal antibody against TROP2, conjugated to KL610023, SKB264, MK-2870, Humanised IgG1 monoclonal antibody against TROP2, conjugated to sulfonylpyrimidine-polyethyleneglycol-lysine-methanesulfonyl belotecan
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: INTRAVENOUS USE
Authorisation status: Not Authorised
MA holder: MERCK & CO. INC.
Paediatric formulation: No
Orphan designation: No

MK-2870

PRD12802980 · Product

Active substance: Sacituzumab Tirumotecan
Substance synonyms: Humanised IgG1 monoclonal antibody against TROP2, conjugated to KL610023, SKB264, MK-2870, Humanised IgG1 monoclonal antibody against TROP2, conjugated to sulfonylpyrimidine-polyethyleneglycol-lysine-methanesulfonyl belotecan
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: INTRAVENOUS USE
Authorisation status: Not Authorised
MA holder: MERCK & CO. INC.
Paediatric formulation: No
Orphan designation: No

MK-4830

PRD11040309 · Product

Active substance: MK-4830
Pharmaceutical form: CONCENTRATE AND SOLVENT FOR CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS USE
Authorisation status: Not Authorised
MA holder: MERCK & CO. INC.
Paediatric formulation: No
Orphan designation: No

Auxiliary 4

R06A · Product

Pharmaceutical form: -
Route of administration: ORAL
Authorisation status: Authorised
ATC code: R06A — ANTIHISTAMINES FOR SYSTEMIC USE
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Buclizine Hydrochloride

SCP1081917 · ATC

Active substance: Buclizine Hydrochloride
Substance synonyms: Buclizine dihydrochloride
Route of administration: OTHER USE
Authorisation status: Authorised
ATC code: N02BE01 — PARACETAMOL
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Famotidine

SCP127871 · ATC

Active substance: Famotidine
Route of administration: ORAL
Authorisation status: Authorised
ATC code: A02BA03 — FAMOTIDINE
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

H02AB · Product

Pharmaceutical form: PHF00231MIG
Route of administration: OTHER USE
Authorisation status: Authorised
ATC code: H02AB — GLUCOCORTICOIDS
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

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: Giulia Indellicati

Public contact point

Organisation: Merck Sharp & Dohme LLC
Contact name: Giulia Indellicati

Third parties 7

Organisation	City, country	Duties
Almac Clinical Services LLC ORG-100041692	Souderton, United States	Interactive response technologies (IRT)
Frontage Laboratories Inc. ORG-100011515	Exton, United States	Laboratory analysis
PPD Global Central Labs ORG-100046496	Zaventem, Belgium	Laboratory analysis
Signant Health Management Limited ORG-100040504	Reading, United Kingdom	E-data capture
Clario ORL-000001148	Philadelphia, United States	Laboratory analysis
Parexel International Corp. ORG-100007310	Auburndale, United States	Other
Icon Clinical Research Limited ORG-100008322	Dublin 18, Ireland	Other

Locations

3 EU/EEA countries · 8 investigational sites

By country

Country	MS status	Planned subjects	Sites
Germany	Ongoing, recruiting	5	2
Italy	Ongoing, recruiting	4	5
Norway	Ongoing, recruiting	1	1
Rest of world Thailand, Turkey, Brazil, Korea, Republic of, Taiwan, United States, Japan, Singapore, Chile, Switzerland, China	—	68	—

Investigational sites

Germany

2 sites · Ongoing, recruiting

Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR

Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie), Fetscherstrasse 74, Johannstadt-Nord, Dresden

Haematologisch Onkologische Praxis Eppendorf

N/A, Eppendorfer Landstrasse 42, 20249, Hamburg

Italy

5 sites · Ongoing, recruiting

Azienda Ospedaliero Universitaria Pisana

U.O. Oncologia Medica 2, Via Roma 67, 56126, Pisa

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Oncologia Medica, Via Piero Maroncelli 40, 47014, Meldola

Istituto Oncologico Veneto

UOC oncologia 1, Via Gattamelata 64, 35128, Padova

Fondazione IRCCS Istituto Nazionale Dei Tumori

S.S. Oncologia Medica Gastroenterologica, Via Giacomo Venezian 1, 20133, Milan

Ospedale San Raffaele S.r.l.

Oncologia Medica, Via Olgettina 60, 20132, Milan

Norway

1 site · Ongoing, recruiting

Oslo University Hospital HF

Enhet for utprøvende kreftbehandling, Montebello, Ullernchausséen 70, Oslo

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country	Trial start	Recruitment start
Germany	2023-07-21	2024-07-30
Italy	2023-05-16	2024-07-01
Norway	2023-03-28	2023-08-29

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Unexpected event UE-55468

Event date: 2024-10-22
Date aware: 2024-10-22
Submission date: 2024-11-04
Member states affected: Germany, Italy, Norway
Clinical procedures: N/A
Event description: The Sponsor has received information regarding a study participant who experienced Grade 4 keratitis with associated corneal perforation. The participant was then permanently discontinued from sac-TMT due to Grade 4 keratitis with the keratitis still ongoing. This case was reported as a SUSAR in Eudravigilance previously.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 33 files

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

Type	Title	Version
Protocol (for publication)	D1_Protocol_2023-505189-26_SM05_for pub	09R
Protocol (for publication)	D1_Protocol_Master Protocol_SM05_for pub	10R
Protocol (for publication)	D1_Protocol_Master Protocol_SM05-RFI001_for pub	09R
Protocol (for publication)	D4_Copyright Statement_Screen Report_SM03_for pub	04Dec2024
Recruitment arrangements (for publication)	CTIS Placeholder document	3.0
Recruitment arrangements (for publication)	K1_Recruitment Arrangements and IC Procedure_DEU_EN_for pub	1.0
Recruitment arrangements (for publication)	K1_Recruitment Arrangements and IC Procedure_ITA_EN_SM04_for pub	13AUG2025
Recruitment arrangements (for publication)	K1_Recruitment Arrangements and ICF Procedure_NOR_EN_for pub	1.0
Recruitment arrangements (for publication)	K2_Recruitment Doc Patient Brochure_MK-3475-06B_DEU_DE_for pub	15MAR2022
Recruitment arrangements (for publication)	K2_Recruitment Doc Poster_MK-3475-06B_DEU_DE_for pub	15MAR2022
Subject information and informed consent form (for publication)	L1_ICF_FBR consent_DEU_DE_SM03_for pub	0.03
Subject information and informed consent form (for publication)	L1_ICF_FBR consent_ITA_IT_for pub	02
Subject information and informed consent form (for publication)	L1_ICF_FBR consent_NOR_NN_SM03_for pub	0.3
Subject information and informed consent form (for publication)	L1_ICF_FBR consent_NOR_NN_TC_SM03_not pub	0.3
Subject information and informed consent form (for publication)	L1_ICF_FBR data privacy_ITA_IT_for pub	25SEP2024
Subject information and informed consent form (for publication)	L1_ICF_Main addendum disease progression_DEU_DE_for pub	AM01v1.00
Subject information and informed consent form (for publication)	L1_ICF_Main addendum disease progression_ITA_IT_SM04_for pub	AM01v1.00
Subject information and informed consent form (for publication)	L1_ICF_Main addendum disease progression_NOR_NN_for pub	00
Subject information and informed consent form (for publication)	L1_ICF_Main consent_DEU_DE_SM04_for pub	AM03v3.01R
Subject information and informed consent form (for publication)	L1_ICF_Main consent_ITA_IT_SM05_for pub	AM04v4.00
Subject information and informed consent form (for publication)	L1_ICF_Main consent_NOR_NN_SM05_for pub	AM04v4.00
Subject information and informed consent form (for publication)	L1_ICF_Main data privacy_ITA_IT_SM04_for pub	08SEP2025
Subject information and informed consent form (for publication)	L1_ICF_Optional_DILI sample_ITA_IT_SM04_for pub	08SEP2025
Subject information and informed consent form (for publication)	L1_ICF_Optional_pregnant partner data privacy_ITA_IT_for pub	25SEP2024
Subject information and informed consent form (for publication)	L1_ICF_Optional_pregnant partner_ITA_IT_SM05_for pub	16MAR2026
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC RSI_PACLITAXEL Hospira UK LTD_SM05_for pub	28JAN2025
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_Irinotecan_for pub	24JUL2023
Synopsis of the protocol (for publication)	D1_PPLS_2023-505189-26_ITA_IT_SM05_for pub	4.0
Synopsis of the protocol (for publication)	D1_PPLS_2023-505189-26_NOR_NN_SM05_for pub	4.0
Synopsis of the protocol (for publication)	D1_PPLS_2023-505189-26_SM05_for pub	4.0
Synopsis of the protocol (for publication)	D1_Protocol Scientific Synopsis_2023-505189-26_ITA_IT_for pub	4.0R
Synopsis of the protocol (for publication)	D1_Protocol Scientific Synopsis_ITA_IT_for pub	4.0
Synopsis of the protocol (for publication)	D1_Protocol Scientific Synopsis_MK-3475-06B_DEU_DE_for pub	05

Application history

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

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-05-31	Norway	Acceptable 2024-06-24	2024-06-24
2	SUBSTANTIAL MODIFICATION	SM-1	2024-08-10		Acceptable	2024-08-29
3	SUBSTANTIAL MODIFICATION	SM-2	2024-10-18	Norway	Acceptable 2025-02-07	2025-02-10
4	SUBSTANTIAL MODIFICATION	SM-3	2025-03-25	Norway	Acceptable with conditions 2025-06-23	2025-06-23
5	SUBSTANTIAL MODIFICATION	SM-4	2025-10-03	Norway	Acceptable 2025-11-17	2025-11-17
6	SUBSTANTIAL MODIFICATION	SM-5	2026-04-06	Norway	Acceptable 2026-05-26	2026-05-26