IFINATAMAB DERUXTECAN for Esophageal squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic squamous cell carcinoma of the esophagus in first line (1L) setting."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable."}
• {"criterion_text":"- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1."}

Exclusion criteria

• {"criterion_text":"- Has had systemic anticancer therapy for locally advanced unresectable or metastatic esophageal cancer."}
• {"criterion_text":"- Has tumor invasion into organs located adjacent to the esophageal disease site (e.g., aorta or respiratory tract) at an increased risk of fistula."}
• {"criterion_text":"- Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention."}
• {"criterion_text":"- Has clinically significant corneal disease."}
• {"criterion_text":"- HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Has received prior treatment with orlotamab, enoblituzumab, or other humanized anti-B7 homologue 3 (B7-H3)-targeted agents."}
• {"criterion_text":"- Has received prior treatment with a topoisomerase-I inhibitor, including antibody-drug conjugate (ADC)."}
• {"criterion_text":"- Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention."}
• {"criterion_text":"- Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids."}
• {"criterion_text":"- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed."}
• {"criterion_text":"- Has inadequate cardiac function assessed as: - corrected QT interval by Fredericia (QTcF) value >470 msec"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Has peripheral neuropathy ≥ Grade 2."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Has known additional malignancy that is progressing or has required active treatment within the past 3 years."}
• {"criterion_text":"- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis."}
• {"criterion_text":"- Has active autoimmune disease that has required systemic treatment in the past 2 years."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Has active infection requiring systemic therapy."}
• {"criterion_text":"- Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Has had allogeneic tissue/solid organ transplant."}
• {"criterion_text":"- Have not adequately recovered from major surgery or have ongoing surgical complications."}
• {"criterion_text":"- Are incapacitated."}

Primary endpoints

• {"endpoint_text":"- Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase","definition_or_measurement_approach":""}
• {"endpoint_text":"- Percentage of Participants who Experience an Adverse Event (AE)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Percentage of Participants Who Discontinue Study Intervention Due to an AE","definition_or_measurement_approach":""}
• {"endpoint_text":"- Objective Response Rate (ORR)","definition_or_measurement_approach":"ORR: evaluated as assessed by Blinded Independent Central Review (BICR) per RECIST 1.1 for selected dose (as stated in main objectives)."}

Secondary endpoints

• {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":"DOR: To evaluate the DOR as assessed by BICR per RECIST 1.1 for selected dose (per secondary objectives)."}
• {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":"PFS: To evaluate PFS as assessed by BICR per RECIST 1.1 for selected dose (per secondary objectives)."}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"OS: To evaluate OS for selected dose."}
• {"endpoint_text":"- Disease control rate (DCR)","definition_or_measurement_approach":"DCR: To evaluate the DCR as assessed by BICR per RECIST 1.1 for selected dose (per secondary objectives)."}
• {"endpoint_text":"- Maximum plasma concentration (Cmax) of ifinatamab deruxtecan (I-DXd)","definition_or_measurement_approach":"PK measure of I-DXd (Cmax)."}
• {"endpoint_text":"- Time to maximum plasma concentration (Tmax) of I-DXd","definition_or_measurement_approach":"PK measure of I-DXd (Tmax)."}
• {"endpoint_text":"- Area Under the Concentration-Time Curve from Time 0 to Last Measurable Plasma Concentration (AUC0-Last) of I-DXd.","definition_or_measurement_approach":"PK measure of I-DXd (AUC0-Last)."}
• {"endpoint_text":"- Area Under the Concentration-Time Curve from Time 0 to the End of the Dosing Period (AUC-tau) of I-DXd","definition_or_measurement_approach":"PK measure of I-DXd (AUC-tau)."}
• {"endpoint_text":"- The Percentage of participants with antidrug antibodies (ADA) against I-DXd.","definition_or_measurement_approach":"Immunogenicity measure: percentage with ADA against I-DXd."}
• {"endpoint_text":"- The Percentage of participants with treatment-emergent ADA against I-DXd.","definition_or_measurement_approach":"Immunogenicity measure: percentage with treatment-emergent ADA against I-DXd."}

France

Earliest CTIS Part Ii Submission Date

13-03-2025

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

340

Number Of Sites

3

Number Of Participants

15

Germany

Earliest CTIS Part Ii Submission Date

25-02-2025

Latest Decision Or Authorization Date

19-02-2026

Processing Time Days

359

Number Of Sites

4

Number Of Participants

8

Norway

Earliest CTIS Part Ii Submission Date

07-03-2025

Latest Decision Or Authorization Date

17-02-2026

Processing Time Days

347

Number Of Sites

1

Number Of Participants

3

Czechia

Earliest CTIS Part Ii Submission Date

03-03-2025

Latest Decision Or Authorization Date

18-02-2026

Processing Time Days

352

Number Of Sites

1

Number Of Participants

6

Italy

Earliest CTIS Part Ii Submission Date

25-02-2025

Latest Decision Or Authorization Date

17-02-2026

Processing Time Days

357

Number Of Sites

2

Number Of Participants

3

Primary sponsor

Full Name

Merck Sharp & Dohme LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

code:4

Name

Parexel International Corp.

Responsibilities

EUB Call center and medical escalation service

Name

PPD Global Central Labs

Responsibilities

code:4

Name

Bioclinica Inc.

Responsibilities

Central imaging

Name

Almac Clinical Technologies LLC

Responsibilities

code:3

Name

Bioclinica Inc.

Responsibilities

code:8

Third parties

• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"EUB Call center and medical escalation service","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central imaging","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"code:3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"code:8","organisation_type":"Laboratory/Research/Testing facility"}