Substudy 06E: Phase 1/2 Umbrella Study of Combination Therapies in Esophageal Cancer

JRCT ID: jRCT2041240166

Registered date:15/01/2025

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: locally advanced unresectable/metastatic esophageal squamous cell carcinoma
• Date of first enrollment: 30/01/2025
• Target sample size: 15
• Countries of recruitment: USA,Japan,Brazil,Japan,Chile,Japan,Czech Republic,Japan,Germany,Japan,Norway,Japan,Turkey,Japan,France,Japan,Italy,Japan,Switzerland,Japan,China,Japan,Singapore,Japan,Taiwan,Japan,South Korea,Japan,Thailand,Japan
• Study type: Interventional

Intervention(s)

-Arm 1:Pembrolizumab 200 mg, every 3 weeks (q3w), Intravenous Infusion (IV) + chemotherapy (mFOLFOX6:oxaliplatin 85 mg/m^2 + 5-FU 400 mg/m^2 [bolus] plus 2400 mg/m^2 [continuous] + levoleucovorin 200 mg/m^2), every 2 weeks (q2w), IV
-Arm 2:ifinatamab deruxtecan (I-DXd) 12 mg/kg, q3w, IV + pembrolizumab 200 mg, q3w, IV
-Arm 3:I-DXd 12 mg/kg, q3w, IV + pembrolizumab 200 mg, q3w, IV + 5-FU (400 mg/m^2 [bolus] plus 2400 mg/m^2 [continuous] ), q2w + levoleucovorin 200 mg/m^2, q2w, IV
-Arm 4:I-DXd 8 or 12 mg/kg, q3w, IV + pembrolizumab 200 mg, q3w, IV + 5-FU 2400 mg/m^2, q2w, IV + oxaliplatin 60 mg/m^2, q2w, IV

Outcome(s)

Primary Outcome

-Dose-limiting toxicities
-Adverse events
-Objective response

Secondary Outcome

-Duration of response (DOR)
-Progression-free survival (PFS)
-Overall survival (OS)
-Disease control rate (DCR)
-Appropriate PK parameters which may include Cmax, Tmax, AUClast, and AUCtau
-Prevalence of antidrug antibodies (ADA)
-Incidence of ADA

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic squamous cell carcinoma of the esophagus in 1L setting.
-Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology assessment and verified by BICR.
-Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided.
-Participants who have AEs due to previous anticancer therapies must have recovered to <=Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have <=Grade 2 neuropathy are eligible.

Exclude criteria

-Has had systemic anticancer therapy for locally advanced unresectable or metastatic esophageal cancer.
-Has tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula as assessed by investigator.
-Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (clinically significant recurrence requiring an additional intervention within 2 weeks of allocation/randomization).
-Has clinically significant corneal disease.
-HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
-Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
-Prior treatment with orlotamab, enoblituzumab, or other B7-H3-targeted agents.
-Has received prior treatment with a topoisomerase-I inhibitor, including ADC.
-Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention.
-Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.
-Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
-Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
-Has peripheral neuropathy > Grade 2.
-Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
-Known additional malignancy that is progressing or has required active treatment within the past 3 years.
-Known active CNS metastases and/or carcinomatous meningitis.
-Active autoimmune disease that has required systemic treatment in the past 2 years.
-History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, and/or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
-Active infection requiring systemic therapy.
-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 enrollment, severe asthma, severe 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.
-History or current evidence of any condition (eg, but not limited to, known deficiency of the enzyme DPD), therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
-Severe hypersensitivity (>=Grade 3) to treatment with a mAb or known sensitivity or intolerance to pembrolizumab, I-DXd, study chemotherapy agents and/or to any of their excipients, murine proteins, or platinum containing products.
-History of allogeneic tissue/solid organ transplant.
-Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Related Information

• Primary Sponsor: Fujita Tomoko