A Study of Ifinatamab Deruxtecan in Subjects With Advanced or Metastatic ESCC (IDeate-Esophageal01)

Trial Title: A Study of Ifinatamab Deruxtecan in Subjects With Advanced or Metastatic ESCC (IDeate-Esophageal01)

NCT ID: NCT06644781

Condition: Esophageal Squamous Cell Carcinoma

Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Paclitaxel
Docetaxel
Irinotecan

Conditions: Keywords:
Esophageal squamous cell carcinoma
Ifinatamab deruxtecan (I-DXd)
DS7300a

Study type: Interventional

Study phase: Phase 3

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Ifinatamab deruxtecan
Description: Intravenous administration
Arm group label: I-DXd

Other name: I-DXd

Intervention type: Drug
Intervention name: Docetaxel
Description: Intravenous administration
Arm group label: Investigator's Choice of Chemotherapy (ICC)

Intervention type: Drug
Intervention name: Paclitaxel
Description: Intravenous administration
Arm group label: Investigator's Choice of Chemotherapy (ICC)

Intervention type: Drug
Intervention name: Irinotecan
Description: Intravenous administration
Arm group label: Investigator's Choice of Chemotherapy (ICC)

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-containing systemic therapy and an immune checkpoint inhibitor (ICI) compared with investigator's choice of chemotherapy (ICC).

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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: Participants must meet all of the following criteria to be eligible for randomization into the study: 1. Sign and date the informed consent form (ICF) prior to the start of any study-specific qualification procedures. 2. Participants aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old). 3. Has histologically or cytologically documented unresectable locally advanced or metastatic ESCC according to American Joint Committee on Cancer 8th edition staging system on ESCC. 4. 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. 5. The participant must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content as defined in the Laboratory Manual. 6. 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. 7. Has an ECOG PS of 0 or 1 within 7 days prior to Cycle 1 Day 1. 8. Has required baseline local laboratory data within 7 days prior to the start of study drug administration. Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor administration is not allowed within 2 weeks prior to screening laboratory tests. Adequate organ function as defined in the study protocol. 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. Previously discontinued an antibody-drug conjugate that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities. 3. Has received any topoisomerase inhibitor within the past 6 months. 4. Has histologically or cytologically confirmed adenosquamous carcinoma subtype. 5. Is ineligible to all the chemotherapies in the comparator arm due to prior progression or intolerance. Participants 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. 6. 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. 7. 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. 8. Has an inadequate washout period before randomization as defined in the protocol. 9. Has any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event, or pulmonary embolism. 10. Has a clinically significant corneal disease. 11. Has an uncontrolled or significant cardiovascular disease as described in the protocol. 12. 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. 13. 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. 14. 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: February 28, 2025

Completion date: October 30, 2029

Lead sponsor:
Agency: Daiichi Sankyo
Agency class: Industry

Collaborator:
Agency: Merck Sharp & Dohme LLC
Agency class: Industry

Source: Daiichi Sankyo

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06644781