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.
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
Significant cardiopulmonary disease and recent cardiac events
History of major organ autoimmune diseases
Acute or chronic infections
Sequential
VIR-5818
DrugAdministered as IV infusion
pembrolizumab
DrugAdministered as IV infusion
Incidence of dose-limiting toxicity - Part 1 and Part 2
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)- Parts 1, 2, 3, and 4
Objective Response Rate (ORR) - Part 3 and Part 4
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
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.
ORR - Part 3 and Part 4
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
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)
PK parameter: Maximum plasma concentration (Cmax)
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Vir Biotechnology, Inc.
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
