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

Phase 3RecruitingNCT06644781

Daiichi Sankyo510 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

510

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: From the date of randomization to the date of death due to any cause, up to approximately 54 months

Secondary Outcomes

Progression-free survival (PFS)

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.

Time frame: 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)

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.

Time frame: 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)

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.

Time frame: 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)

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.

Time frame: 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)

Time frame: Baseline up to 54 months

Change from baseline in European Organisation for Research and Treatment of Cancer Esophageal Cancer Module Score (EORTC OES18)

Time frame: Baseline up to 54 months

Incidence of Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)

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/incapacity, is a congenital anomaly/birth defect, is an important medical event, or may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes noted. AESIs will also be assessed. AEs will be coded using MedDRA and will be graded using NCI-CTCAE v5.0.

Time frame: Baseline up to 54 months

Percentage of Participants Who Have Treatment-emergent ADA

Anti-drug antibodies (ADAs) will be measured in the plasma using a validated assay.

Time frame: Baseline up to 54 months

Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for I-DXd

Plasma pharmacokinetic parameters will be assessed using noncompartmental methods.

Time frame: 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 54 mths: BI (each cycle is 21 days)

Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for Total Anti-B7-H3 Antibody

Plasma pharmacokinetic parameters will be assessed using noncompartmental methods.

Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for MAAA-1181a

Plasma pharmacokinetic parameters will be assessed using noncompartmental methods.

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

Overview

Conditions

Interventions

Eligibility

Locations (132)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts