NCT06644781

Brief Summary

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).

Trial Health

88
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
510

participants targeted

Target at P50-P75 for phase_3

Timeline
42mo left

Started Mar 2025

Longer than P75 for phase_3

Geographic Reach
13 countries

88 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress24%
Mar 2025Nov 2029

First Submitted

Initial submission to the registry

October 10, 2024

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 16, 2024

Completed
5 months until next milestone

Study Start

First participant enrolled

March 27, 2025

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2028

Expected
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2029

Last Updated

January 12, 2026

Status Verified

January 1, 2026

Enrollment Period

3.2 years

First QC Date

October 10, 2024

Last Update Submit

January 9, 2026

Conditions

Keywords

Esophageal squamous cell carcinomaIfinatamab deruxtecan (I-DXd)DS-7300a

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (11)

  • Progression-free survival (PFS)

    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)

    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)

    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)

    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

  • +6 more secondary outcomes

Study Arms (2)

I-DXd

EXPERIMENTAL

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

Investigator's Choice of Chemotherapy (ICC)

ACTIVE COMPARATOR

Participants who are randomized to receive an intravenous infusion of investigator's choice of chemotherapy (docetaxel, paclitaxel, and irinotecan HCl).

Drug: DocetaxelDrug: PaclitaxelDrug: Irinotecan hydrochloride (HCl)

Interventions

Intravenous administration

Also known as: I-DXd
I-DXd

Intravenous administration

Investigator's Choice of Chemotherapy (ICC)

Intravenous administration

Investigator's Choice of Chemotherapy (ICC)

Intravenous administration

Investigator's Choice of Chemotherapy (ICC)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participants must meet all of the following criteria to be eligible for randomization into the study:
  • Participants aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is \>18 years old).
  • Has histologically or cytologically documented unresectable locally advanced or metastatic ESCC according to American Joint Committee on Cancer 8th edition staging system on ESCC.
  • 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.
  • The participant must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content as defined in the Laboratory Manual.
  • 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.
  • Has an ECOG PS of 0 or 1 within 7 days prior to Cycle 1 Day 1.

You may not qualify if:

  • Participants who meet any of the following criteria will be disqualified from entering the study:
  • Has received prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents, including I-DXd.
  • Has received any topoisomerase inhibitor.
  • Has histologically or cytologically confirmed adenosquamous carcinoma subtype.
  • Is ineligible to all the chemotherapies in the comparator arm due to prior progression or intolerance.
  • 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.
  • 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.
  • Has any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event, or pulmonary embolism.
  • Has a clinically significant corneal disease.
  • 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.
  • 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (88)

Providence Medical Foundation

Fullerton, California, 92835, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

RECRUITING

Baptist Cancer Center

Memphis, Tennessee, 38120, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

John Peter Smith Hospital

Fort Worth, Texas, 76104, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Institut Jules Bordet

Brussels, 1070, Belgium

RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

RECRUITING

Antwerp University Hospital

Edegem, 2650, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

Anyang Cancer Hospital

Anyang, 455000, China

RECRUITING

Beijing Cancer Hospital

Beijing, 100142, China

RECRUITING

Jilin Cancer Hospital

Changchun, 130000, China

RECRUITING

Changzhou Cancer Hospital

Changzhou, 213001, China

RECRUITING

Sichuan cancer hospital

Chengdu, 610041, China

RECRUITING

West China Hospital Sichuan University

Chengdu, 610041, China

RECRUITING

Fujian Cancer Hospital

Fuzhou, 350015, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, 150081, China

RECRUITING

The First Affiliated Hospital of Fujian Medical University

Hefei, 230088, China

RECRUITING

Jinan Central Hospital

Jinan, 250013, China

RECRUITING

Shandong Cancer Hospital

Jinan, 250117, China

RECRUITING

Affiliated Hospital of Jining Medical University

Jining, 272029, China

RECRUITING

Guangxi Medical University Affiliated Tumor Hospital

Nanning, 530021, China

RECRUITING

Liaoning Cancer Hospital and Institute

Shenyang, 110042, China

RECRUITING

Tianjin Medical University Cancer Institute and Hospital

Tianjin, 453000, China

RECRUITING

The First Affiliated Hospital of Xinxiang Medical University

Weihui, 453100, China

RECRUITING

Hubei Cancer Hospital

Wuhan, 430000, China

RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430022, China

RECRUITING

Zhongshan Hospital Xiamen University

Xiamen, 361004, China

RECRUITING

Subei Peoples Hospital

Yangzhou, 225001, China

RECRUITING

Sainte Catherine Institut du cancer Avignon en Provence

Avignon, 84918, France

RECRUITING

CHU Brest - Hôpital de la Cavale Blanche

Brest, 29609, France

RECRUITING

Institut Régional du Cancer de Montpellier

Montpellier, 34298, France

RECRUITING

Hôpital Européen Georges Pompidou

Paris, 75015, France

RECRUITING

CHU Poitiers - Hôpital la Milétrie

Poitiers, 86000, France

RECRUITING

Unité de recherche clinique ICANS

Strasbourg, 67033, France

RECRUITING

CHU Toulouse Rangueil Service dOncologie médicale

Toulouse, 31059, France

RECRUITING

Krankenhaus Nordwest GmbH

Frankfurt am Main, 60488, Germany

RECRUITING

Hämatologisch Onkologische Praxis Eppendorf HOPE

Hamburg, 20249, Germany

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Azienda Ospedaliera Universitaria Luigi Vanvitelli

Naples, 80131, Italy

RECRUITING

IOV - Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

RECRUITING

Fondazione Policlinico Gemelli

Rome, 00168, Italy

RECRUITING

National Cancer Center Hospital

Chūōku, 104-0045, Japan

RECRUITING

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa, 277-8577, Japan

RECRUITING

Kagawa University Hospital

Kita-gun, 761-0793, Japan

RECRUITING

Kobe City Hospital Organization Kobe City Medical Center General Hospital

Kobe, 650-0047, Japan

RECRUITING

Cancer Institute Hospital of JFCR

Kōtoku, 135-8550, Japan

RECRUITING

Shikoku Cancer Center

Matsuyama, 791-0280, Japan

RECRUITING

Aichi Cancer Center

Nagoya, 464-8681, Japan

RECRUITING

Osaka International Cancer Institute

Osaka, 541-8567, Japan

RECRUITING

Kindai University Hospital

Ōsaka-sayama, 589-8511, Japan

RECRUITING

Saitama Cancer Center

Saitama, 362-0806, Japan

RECRUITING

Hokkaido University Hospital

Sapporo, 060-8648, Japan

RECRUITING

SHOWA Medical University Hospital

Shinagawa-ku, 142-8666, Japan

RECRUITING

Keio University Hospital

Shinjuku-ku, 160-8582, Japan

RECRUITING

The University of Osaka Hospital

Suita-shi, 565-0871, Japan

RECRUITING

Shizuoka Cancer Center

Sunto-gun, 411-8777, Japan

RECRUITING

Kanagawa Cancer Center

Yokohama, 241-8515, Japan

RECRUITING

Erasmus MC

Rotterdam, 3015 GD, Netherlands

RECRUITING

Zanamed Medical Clinic Sp z o o

Lublin, 20-362, Poland

RECRUITING

Mazowiecki Szpital Wojewódzki

Siedlce, 08-110, Poland

RECRUITING

Memorial Healthcare International S R L

Bucharest, 13823, Romania

RECRUITING

S.C Radiotherapy Center Cluj S.R.L

Comuna Floresti, 407280, Romania

RECRUITING

Centrul de Oncologie Sfantul Nectarie Craiova

Craiova, 200542, Romania

RECRUITING

S.C. Sigmedical Services SRL

Suceava, 720284, Romania

RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, 700-721, South Korea

RECRUITING

National Cancer Center

Goyang-sisouth, 10408, South Korea

RECRUITING

Chonnam National University Hwasun Hospital

Hwasun-gun, 58128, South Korea

RECRUITING

Gachon University Gil Medical Center

Incheon, 21565, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 3722, South Korea

RECRUITING

Asan Medical Center

Seoul, 5505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 6351, South Korea

RECRUITING

The Catholic University of Korea, Seoul St. Marys Hospital

Seoul, 6591, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, 8308, South Korea

RECRUITING

Hospital Universitario de Burgos

Burgos, 9006, Spain

RECRUITING

Hospital General Universitario de Elche

Elche, 3203, Spain

RECRUITING

Hospital Univ Regional de Málaga Hosp Civil

Málaga, 29010, Spain

RECRUITING

Complejo Hospitalario Universitario de Orense

Ourense, 32005, Spain

RECRUITING

Hospital Universitario de Navarra

Pamplona, 31008, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

RECRUITING

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 833, Taiwan

RECRUITING

China Medical University Hospital

Taichung, 40447, Taiwan

NOT YET RECRUITING

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100225, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

DocetaxelPaclitaxelIrinotecan

Condition Hierarchy (Ancestors)

Carcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms, Squamous CellEsophageal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesCamptothecinAlkaloidsHeterocyclic Compounds

Central Study Contacts

Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 10, 2024

First Posted

October 16, 2024

Study Start

March 27, 2025

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

November 1, 2029

Last Updated

January 12, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

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/

Shared Documents
STUDY PROTOCOL, SAP, ICF
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.
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.
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