To Access the Safety and Effects of Intravenous Administration of VIR-5818 Alone and in Combination With Pembrolizumab in Adult Participants With Locally Advanced or Metastatic HER2-Expressing Cancers
- 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.
- Short title
- To Access the Safety and Effects of Intravenous Administration of VIR-5818 Alone and in Combination With Pembrolizumab in Adult Participants With Locally Advanced or Metastatic HER2-Expressing Cancers
- Official title
- 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
- Control arm
- Open label
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Recruiting
- Phase
- Phase 1/Phase 2
- Study type
- Interventional
- Completion date
- 2028-04-01
- First posted
- 2022-05-02
- Registry last updated
- 2026-08-19
- Primary completion date
- 2028-04-01
- Start date
- 2022-04-13
- Participants
- Participant count basis
- Estimated
- Planned participants
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Vir Biotechnology, Inc.
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT05356741
- ClinicalTrials.gov ID
- NCT05356741
- Registry record
- Open registry record
- Allocation
- Not randomised
- Model
- Sequential
- Purpose
- Treatment
- Masking
- No masking
Incidence of dose-limiting toxicity - Part 1 and Part 2
Timeframe: 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
Timeframe: Up to approximately 55 months
Objective Response Rate (ORR) - Part 3 and Part 4
Timeframe: 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
Timeframe: 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.
ORR - Part 3 and Part 4
Timeframe: 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
Timeframe: 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)
Timeframe: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Maximum plasma concentration (Cmax)
Timeframe: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Minimum serum concentration (Cmin)
Timeframe: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Clearance (CL)
Timeframe: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Volume of distribution at steady-state (Vss)
Timeframe: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Accumulation ratio
Timeframe: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Half-life (t1/2)
Timeframe: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
Incidence of anti-drug antibodies (ADAs) to VIR-5818
Timeframe: Multiple timepoints at specified cycles (1 Cycle = 21 days) up to approximately 55 months
All parts: Disease control rate (DCR)
Timeframe: Up to approximately 55 months
defined as CR+PR+ Stable Disease (SD) per RECIST v 1.1
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Healthy volunteers
- No
- 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
The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
- City of Hope National Medical CenterDuarte, United StatesRecruiting
- Investigational site number #100Melbourne, AustraliaActive, not recruiting
- Investigational site number #101Randwick, AustraliaRecruiting
- Investigational site number #150Toulouse, FranceRecruiting
- Investigational site number #200Porto, PortugalRecruiting
- Investigational site number #257Madrid, SpainRecruiting
- Investigational site number #255Barcelona, SpainRecruiting
- Investigational site number #251Barcelona, SpainRecruiting
- Investigational site number #254Madrid, SpainRecruiting
- Investigational site number #252Madrid, SpainRecruiting
- Investigational site number #250Pamplona, SpainRecruiting
- Investigational site number #253Pozuelo de Alarcón, SpainRecruiting
Other registry identifiers
- MK-3475-D14