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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 Jul 2025 → ongoing

Decision date (initial)

2025-06-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo, Inc.

External identifiers

EU CT number

2023-509630-19-00

ClinicalTrials.gov

NCT06644781

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To evaluate the OS benefit of I-DXd compared with investigator’s choice of chemotherapy (ICC)

Secondary objectives 8

1. To evaluate the PFS benefit of I-DXd compared with ICC
2. To evaluate the ORR benefit of I-DXd compared with ICC
3. To further evaluate the efficacy of I-DXd compared with ICC
4. To evaluate PRO endpoints for I-DXd compared with ICC
5. To assess the safety and tolerability of I-DXd
6. To assess the immunogenicity of I-DXd
7. To evaluate B7-H3 protein expression in tumor tissue and its relationship with I-DXd efficacy
8. To characterize the PK of I-DXd (only for subjects randomized to the I-DXd group)

Conditions and MedDRA coding

Esophageal Squamous Cell Carcinoma (ESCC)

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, European Medicines Agency, Food And Drug Administration

Plan to share 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/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Subjects 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
3. Has disease progression post platinum-based and 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 subject must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content.
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.
6. Has an ECOG PS of 0 or 1 within 7 days prior to Cycle 1 Day 1.

Exclusion criteria 11

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 or neuroendocrine features in >30% of tumor tissue.
4. Is ineligible to all the chemotherapies in the comparator arm due to prior progression or intolerance. Subjects who received paclitaxel or docetaxel in definitive chemoradiotherapy or neoadjuvant/adjuvant treatment (chemotherapy or chemoradiotherapy) settings whose disease progressed after 6 months of treatment completion are eligible.
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, or other arterial thromboembolic event.
8. Has a clinically significant corneal disease.
9. Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD or ILD 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. OS is defined as the time interval from the date of randomization to the date of death due to any cause.

Secondary endpoints 9

1. PFS is defined as the time interval from the date of randomization to the first date of disease progression as determined by BICR per RECIST v1.1 or death due to any cause, whichever occurs first.
2. ORR is defined as the proportion of subjects with a BOR of confirmed CR or confirmed PR as assessed by BICR per RECIST v1.1.
3. 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. TTR is defined as the time from randomization to the date of the first documentation of objective response by BICR assessment in responders (BOR of confirmed CR or confirmed PR).
4. DCR is defined as the proportion of subjects with a BOR of confirmed CR, confirmed PR, or SD according to RECIST v1.1 and will be determined by BICR assessment review of tumor scans.
5. The following subscales from validated instruments will be used to assess PROs: EORTC QLQ-C30 – Global Health Status/Quality of Life scale, physical functioning, and fatigue EORTC OES18 – Dysphagia, trouble with eating, reflux, and pain. Change in scores from baseline throughout the Treatment Period will be measured for each scale.
6. Incidence of TEAEs, serious TEAEs, and AESIs graded according to the NCI‑CTCAE v5.0, including deaths, changes from baseline in vital signs, clinical laboratory results, ECGs, and ECHO/MUGA.
7. ADA measured in plasma with a validated assay. ADA prevalence: The proportion of subjects who are ADA positive at any point in time (including pre existing ADA at baseline and treatment emergent ADA). ADA incidence: The proportion of subjects having treatment emergent ADA. Titer and neutralizing antibodies will be determined when the ADA is positive.
8. B7-H3 protein expression in tumor tissue at baseline as determined by IHC and correlation with OS and other efficacy endpoints
9. Plasma concentrations at each time point and PK parameters (Cmax, Tmax, AUClast, and AUCtau) for I DXd, total anti B7-H3 antibody, and DXd in the full PK subset.

Investigational products

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

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 15

Locations

11 EU/EEA countries · 84 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 213 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