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Evaluating ifinatamab deruxtecan for advanced esophageal cancer

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)

Phase 3 Interventional Daiichi Sankyo · NCT06644781

This study is testing a new drug called ifinatamab deruxtecan to see if it helps people with advanced esophageal cancer who haven't responded to other treatments live longer and feel better compared to those getting standard chemotherapy.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment510 (estimated)
Ages18 Years and up
SexAll
SponsorDaiichi Sankyo Industry-sponsored
Drugs / interventionsorlotamab, enoblituzumab, chemotherapy, prednisone, ifinatamab
Locations88 sites (Fullerton, California and 87 other locations)
Trial IDNCT06644781 on ClinicalTrials.gov

What this trial studies

This study assesses the efficacy and safety of ifinatamab deruxtecan (I-DXd) in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have previously progressed after platinum-based chemotherapy and immune checkpoint inhibitors. The primary goal is to compare the overall survival of patients receiving I-DXd versus those receiving investigator's choice of chemotherapy. Secondary objectives include evaluating progression-free survival and objective response rates. Participants must provide adequate tumor samples and have measurable lesions as defined by imaging criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable locally advanced or metastatic ESCC who have progressed after prior treatments.

Not a fit: Patients with resectable ESCC or those who have not received prior platinum-based chemotherapy and immune checkpoint inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced esophageal cancer who have limited treatment choices.

How similar studies have performed: Other studies have shown promising results with similar targeted therapies in advanced cancer settings, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Fullerton, California and 87 other locations

+38 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Esophageal Squamous Cell CarcinomaEsophageal squamous cell carcinomaIfinatamab deruxtecanDS-7300a
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.