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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)

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

Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial_jp@daiichisankyo.com

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial_jp@daiichisankyo.com

Pending

Feb. 03, 2025

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

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.

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, Sjogren'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.

Both

Esophageal Squamous Cell Carcinoma

- Experimental: I-DXd
Participants who are randomized to receive an intravenous infusion of I-DXd 12 mg/kg on Day 1 of every 21-day cycle (Q3W).
- Active Comparator: Investigator's Choice of Chemotherapy (ICC)
Participants who are randomized to receive an intravenous infusion of investigator's choice of chemotherapy (docetaxel or paclitaxel).

1. Overall Survival (OS) [Time Frame: 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.

1. Progression-free survival (PFS) [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 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.

2. Objective Response Rate (ORR) [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
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.

3. Duration of Response (DoR) [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 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.

4. Disease Control Rate (DCR) [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 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.

5. 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 49 months]

6. Change from baseline in European Organisation for Research and Treatment of Cancer Esophageal Cancer Module Score (EORTC OES18) [Time Frame: Baseline up to 49 months]

7. Incidence of Treatment-emergent Adverse Events (TEAEs), serious TEAEs, and Adverse Events of Special Interests (AESIs) [Time Frame: 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/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.

8. Percentage of Participants Who Have Treatment-emergent ADA [Time Frame: Baseline up to49 months]
Anti-drug antibodies (ADAs) will be measured in the plasma using a validated assay.

9. Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for I-DXd [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 49 mths: BI (each cycle is 21 days)]
Plasma pharmacokinetic parameters will be assessed using noncompartmental methods.

10. Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for Total Anti-B7-H3 Antibody [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 6hrpostdose; 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.

11. Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for MAAA-1181a [TimeFrame: 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.

Yes

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/ Supporting Information: - Study Protocol - Statistical Analysis Plan (SAP) - Informed Consent Form (ICF) Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication. Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent. URL: https://vivli.org/ourmember/daiichi-sankyo/

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