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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced or Metastatic HER2-Expressing Cancers
• Intervention / Treatment: Drug: pembrolizumab; Drug: VIR-5818

• Study Type: Interventional
• Enrollment (Estimated): 645
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Inquiry; Phone Number: 415-654-5281; Email: clinicaltrials@vir.bio

Study Locations

• Australia
  • Randwick, Australia, 2031
    • Recruiting
    • Investigational site number #101
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Investigational site number #100
• France
  • Toulouse, France, 31059
    • Recruiting
    • Investigational site number #150
• Portugal
  • Porto, Portugal, 4200-072
    • Recruiting
    • Investigational site number #200
• Spain
  • Barcelona, Spain, 08023
    • Recruiting
    • Investigational site number #255
  • Barcelona, Spain, 08035
    • Recruiting
    • Investigational site number #251
  • Madrid, Spain, 28027
    • Recruiting
    • Investigational site number #254
  • Madrid, Spain, 28050
    • Recruiting
    • Investigational site number #252
  • Pamplona, Spain, 31008
    • Recruiting
    • Investigational site number #250
  • Pozuelo de Alarcón, Spain, 28223
    • Recruiting
    • Investigational site number #253

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 (dose escalation); Participants will receive single-agent VIR-5818	Drug: VIR-5818; Administered as IV infusion
Experimental: Part 2 (dose escalation); Participants will receive VIR-5818 plus pembrolizumab	Drug: pembrolizumab; Administered as IV infusion; Other Names: KEYTRUDA®; Drug: VIR-5818; Administered as IV infusion
Experimental: Part 3 (dose expansion); Participants will receive single-agent VIR-5818	Drug: VIR-5818; Administered as IV infusion
Experimental: Part 4 (dose expansion; Participants will receive VIR-5818 plus pembrolizumab	Drug: pembrolizumab; Administered as IV infusion; Other Names: KEYTRUDA®; Drug: VIR-5818; Administered as IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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).	Up to approximately 55 months
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.	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)	defined as CR+PR+ Stable Disease (SD) per RECIST v 1.1	Up to approximately 55 months

Collaborators and Investigators

• Sponsor: Vir Biotechnology, Inc.
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2022
• Primary Completion (Estimated): August 16, 2027
• Study Completion (Estimated): August 16, 2027

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): May 2, 2022

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 19, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: VIR-5818-V101; MK-3475-D14 (Other Identifier: Merck Sharp & Dohme LLC); KEYNOTE-D14 (Other Identifier: Merck Sharp & Dohme LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No