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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.

Phase 1
Completed
Conditions
Advanced Solid Tumor
Head and Neck Squamous Cell Carcinoma
Interventions
Drug: Bapotulimab (BAY1905254)
Drug: Bapotulimab (BAY1905254) + Pembrolizumab (KEYTRUDA®)
Registration Number
NCT03666273
Lead Sponsor
Bayer
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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

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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose escalation_MonotherapyBapotulimab (BAY1905254)Patients with solid tumor types considered immunosensitive
Dose escalation_Combination therapyBapotulimab (BAY1905254) + Pembrolizumab (KEYTRUDA®)Patients with solid tumor types considered immunosensitive
Expansion HNSCC_Combination therapyBapotulimab (BAY1905254) + Pembrolizumab (KEYTRUDA®)Patients with head and neck squamous cell carcinoma (HNSCC)
Primary Outcome Measures
NameTimeMethod
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
Maximum tolerated dose (MTD) of BapotulimabUp to 58 months
Cmax of Bapotulimab after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mgUp to 504 hours after drug in Cycle 1

Maximum plasma concentration after single dose

AUC of Bapotulimab after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mgUp to 504 hours after drug in Cycle 1

Area under the plasma concentration curve after single dose

Secondary Outcome Measures
NameTimeMethod
Incidence of positive anti-drug antibody titer for BapotulimabUp to 58 months
Best overall response rateUp to 58 months

Determined by RECIST 1.1

Recommended dose of Bapotulimab for Phase 2Up to 58 months
Cmax,md after multiple dosing (Cycle 3) for cohorts receiving doses ≥ 20 mgUp to 504 hours after drug in Cycle 3

Maximum plasma concentration after multiple doses

AUC after multiple dosing (Cycle 3) for cohorts receiving doses ≥ 20 mgUp to 504 hours after drug in Cycle 3

Area under the plasma concentration curve after multiple doses

Trial Locations

Locations (8)

South Texas Accelerated Research Therapeutics | START San Antonio

🇺🇸

San Antonio, Texas, United States

Ohio State University

🇺🇸

Columbus, Ohio, United States

University of Arizona Cancer Center

🇺🇸

Tucson, Arizona, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

University of Chicago Hospitals

🇺🇸

Chicago, Illinois, United States

University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

University Hospitals Cleveland Medical Center

🇺🇸

Cleveland, Ohio, United States

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