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 Pembolizumab in Head and Neck Cancer That Has Returned or is Discovered to be Metastatic and is Expressing PDL1.

Sponsor

Bayer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03666273

Collaborator

Merck Sharp & Dohme LLC (Industry)

120

Enrollment

Locations

Arms

85.6

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Sep 12, 2018

Anticipated Primary Completion Date :

Oct 30, 2023

Anticipated Study Completion Date :

Oct 30, 2025

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

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

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 [Up 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 mg [Up to 504 hours after drug in Cycle 1]
Area under the plasma concentration curve after single dose
Maximum tolerated dose (MTD) of Bapotulimab [Up to 58 months]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center	Tucson	Arizona	United States	85724
2	University of Southern California	Los Angeles	California	United States	90033
3	Yale University School of Medicine	New Haven	Connecticut	United States	06510
4	University of Chicago Hospitals	Chicago	Illinois	United States	60637
5	Norton Healthcare	Louisville	Kentucky	United States	40202
6	Henry Ford Health System	Detroit	Michigan	United States	48202
7	Dartmouth Hitchock Medical Center	Lebanon	New Hampshire	United States	03756-1000
8	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
9	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
10	Ohio State University	Columbus	Ohio	United States	43210
11	Texas Oncology, PA	Dallas	Texas	United States	75246
12	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
13	Millennium Physicians	Houston	Texas	United States	77090
14	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas	United States	78229
15	UZ Antwerpen	Edegem		Belgium	2650