Locally Advanced or Metastatic HER2-Expressing Cancers
Conditions
Brief summary
This first-in-human (FIH) Phase 1 open-label multicenter dose-escalation and dose-expansion study is designed to evaluate the safety, pharmacokinetics, and preliminary activity of VIR-5818 (Formerly AMX-818) as a single agent and in combination with pembrolizumab in participants with HER2+ tumors across multiple tumor types. The study will be conducted in four parts: * Part 1 (dose escalation): Single-agent VIR-5818 * Part 2 (dose escalation): VIR-5818 plus pembrolizumab * Part 3 (dose expansion): Single-agent VIR-5818 * Part 4 (dose expansion): VIR-5818 plus pembrolizumab The total length of the study, from screening of the first participant to the end of the study, is expected to be approximately 72 months.
Interventions
DRUGVIR-5818
Administered as IV infusion
DRUGpembrolizumab
Administered as IV infusion
Sponsors
Vir Biotechnology, Inc.
Merck Sharp & Dohme LLC
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
* Written informed consent by the participant (or legally acceptable representative if applicable) * Life expectancy of at least 12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Diseases under study, prior lines of therapy, and human epidermal growth factor receptor 2 (HER2) status, per local tests
Exclusion criteria
* Significant cardiopulmonary disease and recent cardiac events * History of major organ autoimmune diseases * Acute or chronic infections The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicity - Part 1 and Part 2 | Up to approximately 21 days (Part 1) and 42 days (Part 2) | — |
| Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)- Parts 1, 2, 3, and 4 | Up to approximately 55 months | — |
| Objective Response Rate (ORR) - Part 3 and Part 4 | Up to approximately 55 months | ORR defined as a Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. |
| Duration of Response (DOR) - Part 3 and Part 4 | Up to approximately 55 months | DOR defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, per RECIST v.1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR - Part 3 and Part 4 | Up to approximately 55 months | ORR defined as defined as a Complete Response (CR) or Partial Response (PR) per Immune Response Evaluation Criteria in Solid Tumors (iRECIST). |
| DOR - Part 3 and Part 4 | Up to approximately 55 months | DOR defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, per iRECIST. |
| Pharmacokinetics (PK) parameter: Area under the concentration-time curve (AUC) | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months | — |
| PK parameter: Maximum plasma concentration (Cmax) | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months | — |
| PK parameter: Minimum serum concentration (Cmin) | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months | — |
| PK parameter: Clearance (CL) | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months | — |
| PK parameter: Volume of distribution at steady-state (Vss) | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months | — |
| PK parameter: Accumulation ratio | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months | — |
| PK parameter: Half-life (t1/2) | Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months | — |
| Incidence of anti-drug antibodies (ADAs) to VIR-5818 | Multiple timepoints at specified cycles (1 Cycle = 21 days) up to approximately 55 months | — |
| All parts: Disease control rate (DCR) | Up to approximately 55 months | defined as CR+PR+ Stable Disease (SD) per RECIST v 1.1 |
Countries
Australia, France, Portugal, Spain, United States
Contacts
CONTACTStudy Inquiry
Outcome results
None listed