Clinical trial NCT03666273: 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.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Head and Neck Squamous Cell Carcinoma
Keywords: HNSCC
Head and Neck Cancer
Immunotherapy
PD1, PDL1, ILDR2
Bapotulimab
Pembrolizumab
Immune checkpoint inhibitor
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2018-09-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of treatment-emergent AEs (TEAEs) including treatment-emergent serious adverse events (TESAEs), adverse events of special interest (AESIs), and dose-limiting toxicities (DLTs)
timeFrame: Up to 58 months
measure: Severity of treatment-emergent AEs (TEAEs) including treatment-emergent serious adverse events (TESAEs), adverse events of special interest (AESIs), and dose-limiting toxicities (DLTs)
timeFrame: Up to 58 months
measure: Cmax of Bapotulimab after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mg
timeFrame: Up to 504 hours after drug in Cycle 1
measure: AUC of Bapotulimab after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mg
timeFrame: Up to 504 hours after drug in Cycle 1
measure: Maximum tolerated dose (MTD) of Bapotulimab
timeFrame: Up to 58 months
Secondary outcomes:
measure: Recommended dose of Bapotulimab for Phase 2
timeFrame: Up to 58 months
measure: Cmax,md after multiple dosing (Cycle 3) for cohorts receiving doses ≥ 20 mg
timeFrame: Up to 504 hours after drug in Cycle 3
measure: AUC after multiple dosing (Cycle 3) for cohorts receiving doses ≥ 20 mg
timeFrame: Up to 504 hours after drug in Cycle 3
measure: Incidence of positive anti-drug antibody titer for Bapotulimab
timeFrame: Up to 58 months
measure: Best overall response rate
timeFrame: Up to 58 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Chicago
country: United States
facility: University of Chicago Hospitals
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics | START San Antonio
state: Texas
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: