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

NCT05356741 | Recruiting Phase 1

• 3 other identifiers: VIR-5818-V101MK-3475-D14KEYNOTE-D14
• Study Type: interventional
• Target: 645
• Locations: 4 countries
• Sites: 10

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.

Conditions

Locally Advanced or Metastatic HER2-Expressing Cancers

Outcome Measures

Primary Outcomes (4)

• 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

  ORR defined as a Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.

  Up to approximately 55 months

• 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.

  Up to approximately 55 months

Secondary Outcomes (11)

• ORR - Part 3 and Part 4

  Up to approximately 55 months

• DOR - Part 3 and Part 4

  Up to approximately 55 months

• 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

Study Arms (4)

Part 1 (dose escalation)

EXPERIMENTAL

Participants will receive single-agent VIR-5818

Drug: VIR-5818

Part 2 (dose escalation)

EXPERIMENTAL

Participants will receive VIR-5818 plus pembrolizumab

Drug: VIR-5818; Drug: pembrolizumab

Part 3 (dose expansion)

EXPERIMENTAL

Participants will receive single-agent VIR-5818

Drug: VIR-5818

Part 4 (dose expansion

EXPERIMENTAL

Participants will receive VIR-5818 plus pembrolizumab

Drug: VIR-5818; Drug: pembrolizumab

Interventions

VIR-5818 DRUG

Administered as IV infusion

Part 1 (dose escalation); Part 2 (dose escalation); Part 3 (dose expansion); Part 4 (dose expansion

pembrolizumab DRUG

Administered as IV infusion

Also known as: KEYTRUDA®

Part 2 (dose escalation); Part 4 (dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vir Biotechnology, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

Investigational site number #100

Melbourne, Victoria, 3000, Australia

RECRUITING

Investigational site number #101

Randwick, 2031, Australia

RECRUITING

Investigational site number #150

Toulouse, 31059, France

RECRUITING

Investigational site number #200

Porto, 4200-072, Portugal

RECRUITING

Investigational site number #255

Barcelona, 08023, Spain

RECRUITING

Investigational site number #251

Barcelona, 08035, Spain

RECRUITING

Investigational site number #254

Madrid, 28027, Spain

RECRUITING

Investigational site number #252

Madrid, 28050, Spain

RECRUITING

Investigational site number #250

Pamplona, 31008, Spain

RECRUITING

Investigational site number #253

Pozuelo de Alarcón, 28223, Spain

RECRUITING

MeSH Terms

Interventions

pembrolizumab

Central Study Contacts

Study Inquiry

CONTACT

415-654-5281; clinicaltrials@vir.bio

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2022
• First Posted: May 2, 2022
• Study Start: April 13, 2022
• Primary Completion (Estimated): August 16, 2027
• Study Completion (Estimated): August 16, 2027
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

ES (6); AU (2); PT (1); FR (1)