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

Phase 3

Not yet recruiting

• Conditions: Esophageal Squamous Cell Carcinoma
• Interventions: Drug: Ifinatamab deruxtecan; Drug: Docetaxel; Drug: Paclitaxel; Drug: Irinotecan

• Registration Number: NCT06644781
• Lead Sponsor: Daiichi Sankyo

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Status Verified: 2024-10
• Study First Submitted: 2024-10-10
• Study First Submitted QC: 2024-10-14
• Last Update Submitted: 2024-10-14
• Study First Posted: 2024-10-16
• Last Update Posted: 2024-10-16
• Study Start: 2025-02-28
• Primary Completion: 2029-05-30
• Study Completion: 2029-10-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 510

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
I-DXd	Ifinatamab deruxtecan	Participants who are randomized to receive an intravenous infusion of I-DXd 12 mg/kg on Day 1 of every 21-day cycle (Q3W).
Investigator's Choice of Chemotherapy (ICC)	Docetaxel	Participants who are randomized to receive an intravenous infusion of investigator's choice of chemotherapy (docetaxel, paclitaxel, and irinotecan).
Investigator's Choice of Chemotherapy (ICC)	Paclitaxel	Participants who are randomized to receive an intravenous infusion of investigator's choice of chemotherapy (docetaxel, paclitaxel, and irinotecan).
Investigator's Choice of Chemotherapy (ICC)	Irinotecan	Participants who are randomized to receive an intravenous infusion of investigator's choice of chemotherapy (docetaxel, paclitaxel, and irinotecan).

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From the date of randomization to the date of death due to any cause, up to approximately 49 months	Overall Survival (OS) is defined as the time interval from the date of randomization to the date of death due to any cause.

Secondary Outcome Measures

Name	Time	Method
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 49 months	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.
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 49 months	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.
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 49 months	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.
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 49 months	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.
Change from baseline in European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire Score (EORTC QLQ-C30)	Baseline up to 49 months
Change from baseline in European Organisation for Research and Treatment of Cancer Esophageal Cancer Module Score (EORTC OES18)	Baseline up to 49 months
Incidence of Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)	Baseline up to 49 months	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/incapacit...
Percentage of Participants Who Have Treatment-emergent ADA	Baseline up to 49 months	Anti-drug antibodies (ADAs) will be measured in the plasma using a validated assay.
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for I-DXd	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)	Plasma pharmacokinetic parameters will be assessed using noncompartmental methods.
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for Total Anti-B7-H3 Antibody	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)	Plasma pharmacokinetic parameters will be assessed using noncompartmental methods.
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for MAAA-1181a	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)	Plasma pharmacokinetic parameters will be assessed using noncompartmental methods.