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

JRCT ID: jRCT2031220197

Registered date:08/07/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Esophageal Squamous Cell Carcinoma (ESCC)
• Date of first enrollment: 27/07/2022
• Target sample size: 12
• Countries of recruitment: France,Japan,Italy,Japan,Singapore,Japan,South Korea,Japan,Taiwan,Japan,Thailand,Japan,Turkey,Japan,Brazil,Japan,Chile,Japan,Norway,Japan,Switzerland,Japan,Germany,Japan
• Study type: Interventional

Intervention(s)

- Pembrolizumab plus chemotherapy
Participants will receive pembrolizumab intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
- Coformulation Favezelimab/Pembrolizumab plus Chemotherapy
Participants will receive coformulation of favezelimab/pembrolizumab administered intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
- Pembrolizumab plus MK-4380 plus Chemotherapy
Participants will receive pembrolizumab intravenously plus MK-4380 plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
- Pembrolizumab plus MK-4380 plus lenvatinib
Participants will receive pembrolizumab intravenously plus MK-4380 plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.

- Pembrolizumab: 200 mg administered via intravenous (IV) infusion every 3 weeks (Q3W)
- Irinotecan: 180 mg/m^2 administered via IV infusion on day 1 of every 14-day cycle.
- Paclitaxel: 80-100 mg/m^2 administered via IV infusion on Days 1, 8 and 15 of every 28 day cycle
- Coformulation favezelimab/pembrolizumab: 800 mg favezelimab + 200 mg pembrolizumab administered via IV infusion on day 1 and then Q3W
- MK-4830: 800 mg administered via IV infusion Q3W
- Lenvatinib: 20 mg administered via oral capsules each day

Outcome(s)

Primary Outcome

- Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase
- Number of Participants Experiencing an Adverse Event (AE) During Safety Lead-in Phase
- Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase
- Objective Response Rate (ORR)

Secondary Outcome

- Progression-Free Survival (PFS)
- Duration of Response (DOR)
- Overall Survival (OS)
- Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase
- Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase

Key inclusion & exclusion criteria

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

Include criteria

- Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable ESCC.
- Has experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy.
- Has an evaluable baseline tumor sample (newly obtained or archival) for analysis
- Participants who have adverse events (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

- Direct invasion into adjacent organs such as the aorta or trachea.
- Has experienced weight loss >10% over approximately 2 months prior to first dose of study therapy.
- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication.
- Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has undergone potentially curative therapy.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Active autoimmune disease that has required systemic treatment in past 2 years
- History of human immunodeficiency virus (HIV) infection
- History of Hepatitis B or known active Hepatitis C virus infection.
- History of allogenic tissue/solid organ transplant.
- Clinically significant cardiovascular disease within 12 months from first dose of study intervention.
- Has risk for significant GI bleeding, such as:
* Has had a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization

Related Information

• Primary Sponsor: Koh Yasuhiro
• Secondary ID(s): NCT05342636