A clinical study of ifinatamab deruxtecan and pembrolizumab with or without chemotherapy in people with esophageal cancer (MK-3475-06E)

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

2 Sep 2025 → ongoing

Decision date (initial)

2025-04-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC · Daiichi Sankyo Inc.

External identifiers

EU CT number

2024-514273-22-00

WHO UTN

U1111-1307-6484

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Pharmacokinetic

1. To evaluate the safety and tolerability of investigational treatment combinations and to establish RP2D for investigational agents.
2. To evaluate the ORR as assessed by BICR per RECIST 1.1 for selected dose.

Secondary objectives 6

1. To evaluate the DOR as assessed by BICR per RECIST 1.1 for selected dose.
2. To evaluate PFS as assessed by BICR per RECIST 1.1 for selected dose.
3. To evaluate OS for selected dose.
4. To evaluate the DCR as assessed by BICR per RECIST 1.1 for selected dose.
5. To characterize the PK of I-DXd in combination with other agents.
6. To characterize the immunogenicity of I-DXd.

Conditions and MedDRA coding

Esophageal squamous cell carcinoma

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic squamous cell carcinoma of the esophagus in first line (1L) setting.
2. Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology assessment and verified by blinded independent central review (BICR). Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
3. Has AEs due to previous anticancer therapies of ≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone replacement are acceptable
4. Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART).
5. Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load.
6. Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.
7. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Exclusion criteria 25

1. Has had systemic anticancer therapy for locally advanced unresectable or metastatic esophageal cancer.
2. Has tumor invasion into organs located adjacent to the esophageal disease site (e.g., aorta or respiratory tract) at an increased risk of fistula.
3. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention.
4. Has clinically significant corneal disease.
5. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease.
6. Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
7. Has received prior treatment with orlotamab, enoblituzumab, or other humanized anti-B7 homologue 3 (B7-H3)-targeted agents.
8. Has received prior treatment with a topoisomerase-I inhibitor, including antibody-drug conjugate (ADC).
9. Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention.
10. Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.
11. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
12. Has inadequate cardiac function assessed as: - corrected QT interval by Fredericia (QTcF) value >470 msec
13. Has clinically significant cardiovascular disease within 6 months from 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.
14. Has peripheral neuropathy ≥ Grade 2.
15. Has 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 to the first dose of study intervention.
16. Has known additional malignancy that is progressing or has required active treatment within the past 3 years.
17. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
18. Has active autoimmune disease that has required systemic treatment in the past 2 years.
19. Has had (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, and or suspected interstitial lung disease (ILD)/pneumonitis that cannot be ruled out by imaging at Screening.
20. Has active infection requiring systemic therapy.
21. Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder.
22. Has severe hypersensitivity (≥Grade 3) to treatment with a monoclonal antibody (mAb) or known sensitivity or intolerance to pembrolizumab, I-DXd, study chemotherapy agents and/or to any of their excipients, murine proteins, or platinum containing products.
23. Has had allogeneic tissue/solid organ transplant.
24. Have not adequately recovered from major surgery or have ongoing surgical complications.
25. Are incapacitated.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase
2. Percentage of Participants who Experience an Adverse Event (AE)
3. Percentage of Participants Who Discontinue Study Intervention Due to an AE
4. Objective Response Rate (ORR)

Secondary endpoints 10

1. Duration of response (DOR)
2. Progression-free survival (PFS)
3. Overall survival (OS)
4. Disease control rate (DCR)
5. Maximum plasma concentration (Cmax) of ifinatamab deruxtecan (I-DXd)
6. Time to maximum plasma concentration (Tmax) of I-DXd
7. Area Under the Concentration-Time Curve from Time 0 to Last Measurable Plasma Concentration (AUC0-Last) of I-DXd.
8. Area Under the Concentration-Time Curve from Time 0 to the End of the Dosing Period (AUC-tau) of I-DXd
9. The Percentage of participants with antidrug antibodies (ADA) against I-DXd.
10. The Percentage of participants with treatment-emergent ADA against I-DXd.

Investigational products

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

Test 2

Comparator 4

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Kanu Sharan

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Kanu Sharan

Third parties 6

Locations

5 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

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

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 55 files

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

Application history

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