Phase 1 Study of BAY1905254 - An Early Clinical Research Study to Evaluate a New Drug Called Bapotulimab (BAY1905254) in the Expansion Cohort in Combination With Pembrolizumab in Head and Neck Cancer That Has Returned or is Discovered to be Metastatic and is Expressing PDL1.

An Open-label, Phase 1, First-in-human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics and Tumor Response Profile of the ILDR2 Function-blocking Antibody BAY1905254 in Patients With Advanced Solid Tumors

This study is being done to learn more about a new drug called Bapotulimab given in combination with Pembrolizumab. The purpose of this study is to learn if this new combination of drugs is safe for the participants, how it affects the body and to try to find the best dose of the new drug to give to participants and to obtain a preliminary assessment of the tumor response efficacy in the recurrent or metastatic Head and Neck Cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumor; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Bapotulimab (BAY1905254); Drug: Bapotulimab (BAY1905254) + Pembrolizumab (KEYTRUDA®)

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School Of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Hospitals
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics | START San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

• Male or female patients aged ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

• Patients must have measurable disease (at least one unidimensional measurable lesion by Computed tomography [CT] or Magnetic resonance imaging [MRI]) per Response evaluation criteria in solid tumors (RECIST) 1.1, and following histologically confirmed, advanced or metastatic solid tumors:

  • Dose escalation: All solid tumor types with a likelihood of sensitivity to immunotherapy, as judged by the investigator.
  • Expansion of Bapotulimab in combination with pembrolizumab in Head and neck squamous cell carcinoma (HNSCC): recurrent or metastatic head and neck squamous cell carcinoma IO-naïve PDL1+/ CPS≥1(PD-L1: Programmed death ligand 1; CPS: Combined positive score).
• Provision of archival tumor tissue at screening is mandatory for all patients in dose escalation.
• For dose escalation, patients: must have received standard therapy or have no standard therapy available or patients have actively refused any treatment which would be regarded standard. Or in the opinion of investigator have been considered ineligible for a particular form of standard therapy on medical grounds.
• Adequate bone marrow, liver and renal function.
• Adequate cardiac function, measured by echocardiography.

Main Exclusion Criteria:

• History of severe immune related adverse effects from prior immunotherapy (CTCAE v.5.0 Grade 4; CTCAE v.5.0 Grade 3 requiring treatment > 4 weeks), except hypothyroidism clinically stable on hormone replacement treatment and controlled type 1 diabetes.
• Severe (CTCAE v.5.0 Grade ≥ 3) infections within 4 weeks before the first study drug administration, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. Clinically active infections (CTCAE v.5.0 > Grade 1) within 2 weeks before the first study drug administration.
• Previous or active myocarditis/myositis in history (independent of cause)
• Active or history of autoimmune disease.
• Known human immunodeficiency virus (HIV) infection.
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Treatment with systemic immunosuppressant medications within 2 weeks before the first study drug administration.
• Ongoing or previous anti-cancer treatment or any immunostimulatory treatment including but not limited to interferons (IFNs), interleukin (IL)-2 and agonists for members of the tumor necrosis factor (TNF) receptor superfamily (e.g. 4-1BB) within 4 weeks before the first study drug administration.
• For dose expansion cohort of Bapotulimab in combination with pembrolizumab in HNSCC: has progressive disease (PD) within six (6) months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation_Monotherapy; Patients with solid tumor types considered immunosensitive	Drug: Bapotulimab (BAY1905254); Intravenous administration of escalating doses of Bapotulimab
Experimental: Dose escalation_Combination therapy; Patients with solid tumor types considered immunosensitive	Drug: Bapotulimab (BAY1905254) + Pembrolizumab (KEYTRUDA®); Intravenous administration of Bapotulimab of fixed dose (expansion), and of a fixed dose of pembrolizumab
Experimental: Expansion HNSCC_Combination therapy; Patients with head and neck squamous cell carcinoma (HNSCC)	Drug: Bapotulimab (BAY1905254) + Pembrolizumab (KEYTRUDA®); Intravenous administration of Bapotulimab of fixed dose (expansion), and of a fixed dose of pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent AEs (TEAEs) including treatment-emergent serious adverse events (TESAEs), adverse events of special interest (AESIs), and dose-limiting toxicities (DLTs)		Up to 58 months
Severity of treatment-emergent AEs (TEAEs) including treatment-emergent serious adverse events (TESAEs), adverse events of special interest (AESIs), and dose-limiting toxicities (DLTs)		Up to 58 months
Cmax of Bapotulimab after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mg	Maximum plasma concentration after single dose	Up to 504 hours after drug in Cycle 1
AUC of Bapotulimab after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mg	Area under the plasma concentration curve after single dose	Up to 504 hours after drug in Cycle 1
Maximum tolerated dose (MTD) of Bapotulimab		Up to 58 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended dose of Bapotulimab for Phase 2		Up to 58 months
Cmax,md after multiple dosing (Cycle 3) for cohorts receiving doses ≥ 20 mg	Maximum plasma concentration after multiple doses	Up to 504 hours after drug in Cycle 3
AUC after multiple dosing (Cycle 3) for cohorts receiving doses ≥ 20 mg	Area under the plasma concentration curve after multiple doses	Up to 504 hours after drug in Cycle 3
Incidence of positive anti-drug antibody titer for Bapotulimab		Up to 58 months
Best overall response rate	Determined by RECIST 1.1	Up to 58 months

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Bayer Study Director, Bayer

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2018
• Primary Completion (Actual): June 16, 2023
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: September 10, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 11, 2018

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Immunotherapy; Pembrolizumab; HNSCC; Immune checkpoint inhibitor; PD1, PDL1, ILDR2; Bapotulimab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 18789; MK-3475-920 (Other Identifier: Merck Sharp & Dohme LLC); 2018-000990-63 (EudraCT Number); KEYNOTE-920 (Other Identifier: Merck Sharp & Dohme LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No