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.

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03666273
• Other study ID #: 18789
• Secondary ID: MK-3475-920KEYNO
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 12, 2018
• Est. completion date: May 31, 2024

Study information

• Verified date: April 2024
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: May 31, 2024
• Est. primary completion date: June 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Bapotulimab (BAY1905254)
Intravenous administration of escalating doses of Bapotulimab
• Bapotulimab (BAY1905254) + Pembrolizumab (KEYTRUDA®)
Intravenous administration of Bapotulimab of fixed dose (expansion), and of a fixed dose of pembrolizumab

Locations

Country	Name	City	State
United States	University of Chicago Hospitals	Chicago	Illinois
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Yale University School of Medicine	New Haven	Connecticut
United States	South Texas Accelerated Research Therapeutics | START San Antonio	San Antonio	Texas
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Maximum tolerated dose (MTD) of Bapotulimab		Up to 58 months
Secondary	Recommended dose of Bapotulimab for Phase 2		Up to 58 months
Secondary	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
Secondary	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
Secondary	Incidence of positive anti-drug antibody titer for Bapotulimab		Up to 58 months
Secondary	Best overall response rate	Determined by RECIST 1.1	Up to 58 months