A Phase 1, Multicenter, Open-Label, First-in-Human Study of the Safety and Pharmacokinetics of VIR-5818 Alone and in Combination With Pembrolizumab in Participants With Locally Advanced or Metastatic HER2-Expressing Cancers
Overview
- Phase
- Phase 1
- Intervention
- VIR-5818
- Conditions
- Locally Advanced or Metastatic HER2-Expressing Cancers
- Sponsor
- Vir Biotechnology, Inc.
- Enrollment
- 645
- Locations
- 10
- Primary Endpoint
- Incidence of dose-limiting toxicity - Part 1 and Part 2
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
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 52 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Part 1 (dose escalation)
Participants will receive single-agent VIR-5818
Intervention: VIR-5818
Part 2 (dose escalation)
Participants will receive VIR-5818 plus pembrolizumab
Intervention: VIR-5818
Part 2 (dose escalation)
Participants will receive VIR-5818 plus pembrolizumab
Intervention: pembrolizumab
Part 3 (dose expansion)
Participants will receive single-agent VIR-5818
Intervention: VIR-5818
Part 4 (dose expansion
Participants will receive VIR-5818 plus pembrolizumab
Intervention: VIR-5818
Part 4 (dose expansion
Participants will receive VIR-5818 plus pembrolizumab
Intervention: pembrolizumab
Outcomes
Primary Outcomes
Incidence of dose-limiting toxicity - Part 1 and Part 2
Time Frame: 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
Time Frame: Up to approximately 55 months
Objective Response Rate (ORR) - Part 3 and Part 4
Time Frame: 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
Time Frame: 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 Outcomes
- 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)
- DOR - Part 3 and Part 4(Up to approximately 55 months)
- ORR - Part 3 and Part 4(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)