Advanced Solid Tumor, Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
HNSCC, Head and Neck Cancer, Immunotherapy, PD1, PDL1, ILDR2, Bapotulimab, Pembrolizumab, Immune checkpoint inhibitor
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.
Interventions
DRUGBapotulimab (BAY1905254)
Intravenous administration of escalating doses of Bapotulimab
DRUGBapotulimab (BAY1905254) + Pembrolizumab (KEYTRUDA®)
Intravenous administration of Bapotulimab of fixed dose (expansion), and of a fixed dose of pembrolizumab
Sponsors
Merck Sharp & Dohme LLC
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) of Bapotulimab | Up to 58 months | — |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed