A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B)

Purpose

This is a Phase 1/2, multicenter, randomized, open-label umbrella platform study to evaluate the safety and efficacy of investigational agents with or without pembrolizumab and/or chemotherapy, for the treatment of participants with second line (2L) esophageal squamous cell carcinoma (ESCC) who have previously been exposed to PD-1/PD-L1 based treatment.

Condition

  • Esophageal Squamous Cell Carcinoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable esophageal squamous cell carcinoma (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-programmed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1) based immune oncology (IO) therapy - Has provided an archival or most recent tumor tissue sample obtained as part of clinical practice - 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

Exclusion 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 severe corneal disease that prevents/delays corneal healing - Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease - Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration - 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 - Participants with human immunodeficiency virus (HIV) with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease - History of allogenic tissue/solid organ transplant - Clinically significant cardiovascular disease within 12 months from first dose of study intervention - Has risk for significant gastrointestinal (GI) bleeding such as a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization, significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Paclitaxel or irinotecan 		Participants 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.
  • Drug: Paclitaxel
    80-100 mg/m^2 IV infusion, administered on days 1, 8, and 15 of every 28-day cycle.
  • Drug: Irinotecan
    180 mg/m^2 IV infusion, administered on day 1 of every 14-day cycle.
Experimental
Pembrolizumab + MK-4830 + paclitaxel or irinotecan 		Participants 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^2 180 mg/m^2 on day 1 every 14-day cycle until PD or discontinuation.
  • Drug: Paclitaxel
    80-100 mg/m^2 IV infusion, administered on days 1, 8, and 15 of every 28-day cycle.
  • Drug: Irinotecan
    180 mg/m^2 IV infusion, administered on day 1 of every 14-day cycle.
  • Biological: Pembrolizumab
    200 mg IV infusion, administered every Q3W up to 35 infusions.
    Other names:
    • MK-3475
    • KEYTRUDA®
  • Biological: MK-4830
    800 mg IV infusion, administered Q3W up to 35 infusions.
    Other names:
    • anti-immunoglobulin-like transcript 4 (anti-ILT4)
Experimental
Pembrolizumab + MK-4830 + lenvatinib 		Participants 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.
  • Biological: Pembrolizumab
    200 mg IV infusion, administered every Q3W up to 35 infusions.
    Other names:
    • MK-3475
    • KEYTRUDA®
  • Biological: MK-4830
    800 mg IV infusion, administered Q3W up to 35 infusions.
    Other names:
    • anti-immunoglobulin-like transcript 4 (anti-ILT4)
  • Drug: Lenvatinib
    20 mg oral administration every day.
    Other names:
    • MK-7902
    • LENVIMA®
Experimental
Sacituzumab tirumotecan 4 mg/kg 		Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation.
  • Biological: Sacituzumab tirumotecan
    4 mg/kg or 5 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.
    Other names:
    • SKB264
    • MK-2870
    • sac-TMT
  • Drug: Antihistamine
    Administered per product label.
  • Drug: H2 Receptor Antagonist
    Administered per product label.
  • Drug: Acetaminophen (or equivalent)
    Administered per product label.
  • Drug: Dexamethasone (or equivalent)
    Administered per product label.
  • Drug: Steroid Mouthwash (dexamethasone or equivalent)
    Administered per product label.
  • Drug: Supportive care measures
    Participants are allowed to take supportive care measures for the management of adverse events associated with study intervention at the discretion of the investigator. Artificial tear drops or ointment may be given as a supportive care for Ocular Surface Toxicity.
Experimental
Sacituzumab tirumotecan 5 mg/kg 		Participants will receive 5 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation.
  • Biological: Sacituzumab tirumotecan
    4 mg/kg or 5 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.
    Other names:
    • SKB264
    • MK-2870
    • sac-TMT
  • Drug: Antihistamine
    Administered per product label.
  • Drug: H2 Receptor Antagonist
    Administered per product label.
  • Drug: Acetaminophen (or equivalent)
    Administered per product label.
  • Drug: Dexamethasone (or equivalent)
    Administered per product label.
  • Drug: Steroid Mouthwash (dexamethasone or equivalent)
    Administered per product label.
  • Drug: Supportive care measures
    Participants are allowed to take supportive care measures for the management of adverse events associated with study intervention at the discretion of the investigator. Artificial tear drops or ointment may be given as a supportive care for Ocular Surface Toxicity.

Recruiting Locations

University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 4927)
Tucson, Arizona 85719
Contact:
Study Coordinator
520-621-2449

UCLA Hematology/Oncology - Santa Monica ( Site 4905)
Los Angeles, California 90404
Contact:
Study Coordinator
310-570-1453

Hematology-Oncology Associates of Central NY, P.C. ( Site 4925)
East Syracuse, New York 13057
Contact:
Study Coordinator
315-472-7504

UPMC Hillman Cancer Center-UPMC ( Site 4904)
Pittsburgh, Pennsylvania 15232
Contact:
Study Coordinator
816-898-9413

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@msd.com

Detailed Description

The master protocol is MK-3475-U06. As of Protocol Amendment 5, the Pembrolizumab Plus MK-4830 Plus Paclitaxel/Irinotecan arm and the Pembrolizumab Plus MK-4830 Plus Lenvatinib arm are no longer actively enrolling participants.