A Study of Ifinatamab Deruxtecan in Subjects With Pretreated Advanced or Metastatic Esophageal Squamous Cell Carcinoma (ESCC) (IDeate-Esophageal01)

A Phase 3, Multicenter, Randomized, Open-label Study of Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Advanced or Metastatic Esophageal Squamous Cell Carcinoma (ESCC) (IDeate-Esophageal01)

This study is designed to assess the efficacy and safety of ifinatamab deruxtecan (I-DXd) in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have experienced disease progression following treatment with a platinum-based systemic therapy and an immune checkpoint inhibitor (ICI) compared with investigator's choice of chemotherapy (ICC).

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Ifinatamab deruxtecan; Drug: Docetaxel; Drug: Paclitaxel; Drug: Irinotecan hydrochloride (HCl)

Detailed Description

The primary objective of this study is to evaluate the overall survival (OS) benefit of I-DXd compared with investigator's choice of chemotherapy (ICC).

The key secondary objectives of the study will evaluate the progression-free survival (PFS) and objective response rate (ORR) benefit of I-DXd compared with ICC.

• Study Type: Interventional
• Enrollment (Estimated): 510
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: 9089926400; Email: CTRinfo_us@daiichisankyo.com

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Recruiting
    • Institut Jules Bordet
  • Brussels, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires Saint-Luc
  • Edegem, Belgium, 2650
    • Recruiting
    • Antwerp University Hospital
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
• China
  • Anyang, China, 455000
    • Recruiting
    • Anyang Cancer Hospital
  • Beijing, China, 100142
    • Recruiting
    • Beijing Cancer Hospital
  • Changchun, China, 130000
    • Recruiting
    • Jilin Cancer Hospital
  • Changzhou, China, 213001
    • Recruiting
    • Changzhou Cancer hospital
  • Chengdu, China, 610041
    • Recruiting
    • Sichuan Cancer Hospital
  • Chengdu, China, 610041
    • Recruiting
    • West China Hospital Sichuan University
  • Fuzhou, China, 350015
    • Recruiting
    • Fujian Cancer Hospital
  • Harbin, China, 150081
    • Recruiting
    • Harbin Medical University Cancer Hospital
  • Hefei, China, 230088
    • Recruiting
    • The First Affiliated Hospital of Fujian Medical University
  • Jinan, China, 250117
    • Recruiting
    • Shandong Cancer Hospital
  • Jinan, China, 250013
    • Recruiting
    • Jinan Central Hospital
  • Jining, China, 272029
    • Recruiting
    • Affiliated Hospital of Jining Medical University
  • Nanning, China, 530021
    • Recruiting
    • Guangxi Medical University Affiliated Tumor Hospital
  • Shenyang, China, 110042
    • Recruiting
    • Liaoning Cancer Hospital and Institute
  • Tianjin, China, 453000
    • Recruiting
    • Tianjin Medical University Cancer Institute and Hospital
  • Weihui, China, 453100
    • Recruiting
    • The First Affiliated Hospital of Xinxiang Medical University
  • Wuhan, China, 430022
    • Recruiting
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Wuhan, China, 430000
    • Recruiting
    • Hubei Cancer Hospital
  • Xiamen, China, 361004
    • Recruiting
    • Zhongshan Hospital Xiamen University
  • Yangzhou, China, 225001
    • Recruiting
    • Subei Peoples Hospital
• France
  • Avignon, France, 84918
    • Recruiting
    • Sainte Catherine Institut du cancer Avignon en Provence
  • Brest, France, 29609
    • Recruiting
    • CHU Brest - Hôpital de la Cavale Blanche
  • Montpellier, France, 34298
    • Recruiting
    • Institut Regional du Cancer de Montpellier
  • Paris, France, 75015
    • Recruiting
    • Hôpital Européen Georges Pompidou
  • Poitiers, France, 86000
    • Recruiting
    • CHU Poitiers - Hopital la Miletrie
  • Strasbourg, France, 67033
    • Recruiting
    • Unité de recherche clinique ICANS
  • Toulouse, France, 31059
    • Recruiting
    • CHU Toulouse Rangueil Service dOncologie médicale
• Germany
  • Frankfurt am Main, Germany, 60488
    • Recruiting
    • Krankenhaus Nordwest GmbH
  • Hamburg, Germany, 20249
    • Recruiting
    • Hämatologisch Onkologische Praxis Eppendorf HOPE
• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Napoli, Italy, 80131
    • Recruiting
    • Azienda Ospedaliera Universitaria Luigi Vanvitelli
  • Padua, Italy, 35128
    • Recruiting
    • Iov - Istituto Oncologico Veneto Irccs
  • Rome, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Gemelli
• Japan
  • Chūōku, Japan, 104-0045
    • Recruiting
    • National Cancer Center Hospital
  • Hiroshima, Japan, 734-8551
    • Recruiting
    • Hiroshima University Hospital
  • Kashiwa, Japan, 277-8577
    • Recruiting
    • National Cancer Center Hospital East
  • Kita-gun, Japan, 761-0793
    • Recruiting
    • Kagawa University Hospital
  • Kobe, Japan, 650-0047
    • Recruiting
    • Kobe City Hospital Organization Kobe City Medical Center General Hospital
  • Kōtoku, Japan, 135-8550
    • Recruiting
    • Cancer Institute Hospital of JFCR
  • Matsuyama, Japan, 791-0280
    • Recruiting
    • Shikoku Cancer Center
  • Nagoya, Japan, 464-8681
    • Recruiting
    • Aichi Cancer Center
  • Osaka, Japan, 541-8567
    • Recruiting
    • Osaka International Cancer Institute
  • Saitama, Japan, 362-0806
    • Recruiting
    • Saitama Cancer Center
  • Sapporo, Japan, 060-8648
    • Recruiting
    • Hokkaido University Hospital
  • Shinagawa-ku, Japan, 142-8666
    • Recruiting
    • SHOWA Medical University Hospital
  • Shinjuku-ku, Japan, 160-8582
    • Recruiting
    • Keio University Hospital
  • Suita-shi, Japan, 565-0871
    • Recruiting
    • The University of Osaka Hospital
  • Sunto-gun, Japan, 411-8777
    • Recruiting
    • Shizuoka Cancer Center
  • Yokohama, Japan, 241-8515
    • Recruiting
    • Kanagawa Cancer Center
  • Ōsaka-sayama, Japan, 589-8511
    • Recruiting
    • Kindai University Hospital
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Erasmus MC
• Poland
  • Lublin, Poland, 20-362
    • Recruiting
    • Zanamed Medical Clinic sp z o o
  • Siedlce, Poland, 08-110
    • Recruiting
    • Mazowiecki Szpital Wojewódzki
• Romania
  • Bucharest, Romania, 13823
    • Recruiting
    • Memorial Healthcare International S R L
  • Comuna Floresti, Romania, 407280
    • Recruiting
    • S.C Radiotherapy Center Cluj S.R.L
  • Craiova, Romania, 200542
    • Recruiting
    • Centrul de Oncologie Sfantul Nectarie Craiova
  • Suceava, Romania, 720284
    • Recruiting
    • S.C. Sigmedical Services SRL
• South Korea
  • Daegu, South Korea, 700-721
    • Recruiting
    • Kyungpook National University Chilgok Hospital
  • Goyang-sisouth, South Korea, 10408
    • Recruiting
    • National Cancer Center
  • Hwasun-gun, South Korea, 58128
    • Recruiting
    • Chonnam National University Hwasun Hospital
  • Incheon, South Korea, 21565
    • Recruiting
    • Gachon University Gil Medical Center
  • Seongnam-si, South Korea, 13620
    • Recruiting
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 6351
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 5505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 3722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 8308
    • Recruiting
    • Korea University Guro Hospital
  • Seoul, South Korea, 6591
    • Recruiting
    • The Catholic University of Korea, Seoul St. Marys Hospital
• Spain
  • Burgos, Spain, 9006
    • Recruiting
    • Hospital Universitario de Burgos
  • Elche, Spain, 3203
    • Recruiting
    • Hospital General Universitario de Elche
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Univ Regional de Málaga Hosp Civil
  • Ourense, Spain, 32005
    • Recruiting
    • Complejo Hospitalario Universitario de Orense
  • Pamplona, Spain, 31008
    • Recruiting
    • Hospital Universitario de Navarra
  • Seville, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen Macarena
• Taiwan
  • Kaohsiung City, Taiwan, 833
    • Recruiting
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan, 40447
    • Not yet recruiting
    • China Medical University Hospital
  • Tainan, Taiwan, 70403
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 100225
    • Recruiting
    • National Taiwan University Hospital
• United States
  • California
    • Fullerton, California, United States, 92835
      • Recruiting
      • Providence Medical Foundation
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Recruiting
      • Baptist Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • John Peter Smith Hospital
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for randomization into the study:

1. Participants aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
2. Has histologically or cytologically documented unresectable locally advanced or metastatic ESCC according to American Joint Committee on Cancer 8th edition staging system on ESCC.
3. Has disease progression post a platinum-based chemotherapy and an ICI treatment per global or local guidelines, with a maximum of 1 prior line of systemic therapy for unresectable advanced or metastatic ESCC.
4. The participant must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content as defined in the Laboratory Manual.
5. Has at least 1 measurable lesion on computed tomography (CT)/magnetic resonance imaging (MRI) according to RECIST v1.1 as assessed by the investigator. Measurable lesions should not be from a previously irradiated site. If the lesion at a previously irradiated site is the only selectable target lesion, a radiological assessment showing significant progression of the irradiated lesion should be provided by the investigator.
6. Has an ECOG PS of 0 or 1 within 7 days prior to Cycle 1 Day 1.

Exclusion Criteria:

Participants who meet any of the following criteria will be disqualified from entering the study:

1. Has received prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents, including I-DXd.
2. Has received any topoisomerase inhibitor.
3. Has histologically or cytologically confirmed adenosquamous carcinoma subtype.
4. Is ineligible to all the chemotherapies in the comparator arm due to prior progression or intolerance.
5. Has tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of bleeding or fistula as assessed by the investigator.
6. Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive or treated brain metastases who are asymptomatic (ie, without neurologic signs or symptoms and not requiring treatment with corticosteroids or anticonvulsants) may be included in the study. Subjects must have a stable neurologic status and discontinue corticosteroid usage for at least 2 weeks prior to Screening.
7. Has any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event, or pulmonary embolism.
8. Has a clinically significant corneal disease.
9. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
10. Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study randomization, severe asthma, chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc), and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc), prior pneumonectomy, or requirement for supplemental oxygen.
11. Is on chronic steroid treatment (dose of 10 mg daily or more prednisone equivalent), except for low-dose inhaled steroids (for asthma/COPD), topical steroids (for mild skin conditions), or intra-articular steroid injections.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I-DXd; Participants who are randomized to receive an intravenous infusion of I-DXd 12 mg/kg on Day 1 of every 21-day cycle (Q3W).	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Active Comparator: Investigator's Choice of Chemotherapy (ICC); Participants who are randomized to receive an intravenous infusion of investigator's choice of chemotherapy (docetaxel, paclitaxel, and irinotecan HCl).	Drug: Docetaxel; Intravenous administration; Drug: Paclitaxel; Intravenous administration; Drug: Irinotecan hydrochloride (HCl); Intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival (OS) is defined as the time interval from the date of randomization to the date of death due to any cause.	From the date of randomization to the date of death due to any cause, up to approximately 54 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for Total Anti-B7-H3 Antibody	Plasma pharmacokinetic parameters will be assessed using noncompartmental methods.	Cycle 1: Before infusion (BI), end of infusion (EOI), 3 hours (hr), 6hr, 24hr, 72hr, 168hr, 336hr, 504hr postdose; Cycle 2: BI and EOI; Cycle 3: BI, EOI, and 6hr postdose; Cycle 4, 5, & every 2 cycles thereafter, up to 49 mths: BI (each cycle is 21 days)
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for MAAA-1181a	Plasma pharmacokinetic parameters will be assessed using noncompartmental methods.	Cycle 1: Before infusion (BI), end of infusion (EOI), 3 hours (hr), 6hr, 24hr, 72hr, 168hr, 336hr, 504hr postdose; Cycle 2: BI and EOI; Cycle 3: BI, EOI, and 6hr postdose; Cycle 4, 5, & every 2 cycles thereafter, up to 49 mths: BI (each cycle is 21 days)
Progression-free survival (PFS)	Progression-free survival (PFS) is defined as the time interval from the date of randomization to the first date of disease progression as determined by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first.	From the date of randomization to the date of disease progression or death due to any cause, whichever occurs first, up to approximately 54 months
Objective Response Rate (ORR)	Objective response rate (ORR) is defined as the proportion of subjects with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) as assessed by BICR per RECIST v1.1.	From the time of first dose of study drug until date of documented disease progression or death, whichever occurs first, up to approximately 54 months
Duration of Response (DoR)	Duration of response (DoR) is defined as the time from the date of first documentation of objective tumor response (CR or PR), which is subsequently confirmed by BICR assessment, to the first documentation of objective tumor progression (confirmed by BICR) or to death due to any cause, whichever occurs first.	From the time of the first dose of study drug until the date of documented disease progression (as assessed by BICR) or death due to any cause, up to approximately 54 months
Disease Control Rate (DCR)	Disease control rate (DCR) is defined as the proportion of participants with a BOR of confirmed CR, confirmed PR, or stable disease (SD) according to RECIST v1.1 and will be determined by BICR assessment review of tumor scans.	From the time of the first dose of study drug until the date of documented disease progression (as assessed by BICR) or death due to any cause, up to approximately 54 months
Change from baseline in European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire Score (EORTC QLQ-C30)		Baseline up to 54 months
Change from baseline in European Organisation for Research and Treatment of Cancer Esophageal Cancer Module Score (EORTC OES18)		Baseline up to 54 months
Incidence of Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)	A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. A serious TEAE is defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event, or may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes noted. AESIs will also be assessed. AEs will be coded using MedDRA and will be graded using NCI-CTCAE v5.0.	Baseline up to 54 months
Percentage of Participants Who Have Treatment-emergent ADA	Anti-drug antibodies (ADAs) will be measured in the plasma using a validated assay.	Baseline up to 54 months
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for I-DXd	Plasma pharmacokinetic parameters will be assessed using noncompartmental methods.	Cycle 1: Before infusion (BI), end of infusion (EOI), 3 hours (hr), 6hr, 24hr, 72hr, 168hr, 336hr, 504hr postdose; Cycle 2: BI and EOI; Cycle 3: BI, EOI, and 6hr postdose; Cycle 4, 5, & every 2 cycles thereafter, up to 54 mths: BI (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: October 10, 2024
• First Submitted That Met QC Criteria: October 14, 2024
• First Posted (Actual): October 16, 2024

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Esophageal squamous cell carcinoma; DS-7300a; Ifinatamab deruxtecan (I-DXd)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Organic Chemicals; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Camptothecin; Alkaloids; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; Irinotecan; Paclitaxel
• Other Study ID Numbers: DS7300-202; 2023-509630-19-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No