Substudy 06B: Phase 1/2 Umbrella Study of Investigational Agents With or Without Pembrolizumab and/or Chemotherapy in Esophageal Cancer

JRCT ID: jRCT2031220582

Registered date:22/01/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Esophageal Squamous Cell Carcinoma (ESCC)
• Date of first enrollment: 06/07/2023
• Target sample size: 13
• Countries of recruitment: China,Japan,USA,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)

- Paclitaxel or irinotecan
Participants will receive paclitaxel 80-100 mg/m^2 intravenously (IV) on days 1, 8, and 15 every 28-day cycle until progressive disease (PD) or discontinuation, or irinotecan 180 mg/m^2 IV on day 1 of every 14-day cycle until PD or discontinuation.

- Pembrolizumab plus MK-4380 plus paclitaxel or irinotecan
Participants will receive pembrolizumab 200 mg IV once every 3 weeks (Q3W) for up to 35 cycles (cycle=21 days) or until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + paclitaxel 80-100 mg/m^2 IV on days 1, 8, and 15 every 28-day cycle until PD or discontinuation or irinotecan 180 mg/m^2 on day 1 every 14-day cycle until PD or discontinuation.

- Pembrolizumab plus MK-4380 plus lenvatinib
Participants will receive pembrolizumab 200 mg IV Q3W up to 35 cycles (cycle=21 days) until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + lenvatinib 20 mg oral administration every day until PD or discontinuation.

- MK-2870
Participants will receive 4 mg/kg of MK-2870 via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation.

Outcome(s)

Primary Outcome

- Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During Safety Lead-in Phase
- Number of Participants Experiencing Adverse Events (AEs) 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, that includes a platinum agent and previous exposure to an anti-PD1/PD-L1 based 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 history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.
- Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease.
- Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
- 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): NCT05319730