Clinical trial NCT06644781: A Study of Ifinatamab Deruxtecan in Subjects With Pretreated Advanced or Metastatic Esophageal Squamous Cell Carcinoma (ESCC) (IDeate-Esophageal01)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: Esophageal squamous cell carcinoma
Ifinatamab deruxtecan (I-DXd)
DS-7300a
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2024-10-16
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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-based 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of randomization to the date of death due to any cause, up to approximately 54 months
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 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
measure: Objective Response Rate (ORR)
timeFrame: 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
measure: Duration of Response (DoR)
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: 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
measure: Change from baseline in European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire Score (EORTC QLQ-C30)
timeFrame: Baseline up to 54 months
measure: Change from baseline in European Organisation for Research and Treatment of Cancer Esophageal Cancer Module Score (EORTC OES18)
timeFrame: Baseline up to 54 months
measure: Incidence of Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)
timeFrame: Baseline up to 54 months
measure: Percentage of Participants Who Have Treatment-emergent ADA
timeFrame: Baseline up to 54 months
measure: Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for I-DXd
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 54 mths: BI (each cycle is 21 days)
measure: Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for Total Anti-B7-H3 Antibody
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)
measure: 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)
Other outcomes:
Locations:
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Kita-gun
country: Japan
facility: Kagawa University Hospital
city: Kobe-shi
country: Japan
facility: Kobe City Hospital Organization Kobe City Medical Center General Hospital
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Matsuyama
country: Japan
facility: Shikoku Cancer Center
city: Nagaizumi-chō
country: Japan
facility: Shizuoka Cancer Center
city: Nagoya
country: Japan
facility: Aichi Cancer Center
city: Osaka-Sayama
country: Japan
facility: Kindai University Hospital
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
city: Suita-shi
country: Japan
facility: The University of Osaka Hospital
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
References: