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.

• ClinicalTrials.gov Identifier: NCT03666273
• Recruitment Status: Active, not recruiting
• First Posted: September 11, 2018
• Last Update Posted: June 1, 2023
• Sponsor: Bayer
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Bayer

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor, Head and Neck Squamous Cell Carcinoma	Drug: Bapotulimab (BAY1905254); Drug: Bapotulimab (BAY1905254) + Pembrolizumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 12, 2018
• Estimated Primary Completion Date: June 16, 2023
• Estimated Study Completion Date: May 31, 2024

Arms and Interventions

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; 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; Intravenous administration of Bapotulimab of fixed dose (expansion), and of a fixed dose of pembrolizumab

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

University of Arizona Cancer Center

Tucson, Arizona, United States, 85724

United States, Connecticut

Yale University School of Medicine

New Haven, Connecticut, United States, 06510

United States, Illinois

University of Chicago Hospitals

Chicago, Illinois, United States, 60637

United States, Michigan

Henry Ford Health System

Detroit, Michigan, United States, 48202

United States, Ohio

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

Ohio State University

Columbus, Ohio, United States, 43210

United States, Texas

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

South Texas Accelerated Research Therapeutics | START San Antonio

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Bayer

Merck Sharp & Dohme LLC

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT03666273
• Other Study ID Numbers: 18789; MK-3475-920 ( Other Identifier: Merck ); 2018-000990-63 ( EudraCT Number )
• First Posted: September 11, 2018
• Last Update Posted: June 1, 2023
• Last Verified: May 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:

HNSCC; Head and Neck Cancer; Immunotherapy; PD1, PDL1, ILDR2; Bapotulimab; Pembrolizumab; Immune checkpoint inhibitor

Additional relevant MeSH terms:

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action