Locally Advanced or Metastatic HER2-Expressing CancersPhase 1/2NCT05356741
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 1/2 study testing VIR-5818 and pembrolizumab in people with Locally Advanced or Metastatic HER2-Expressing Cancers, run by Vir Biotechnology, Inc. at 12 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced or Metastatic HER2-Expressing Cancers
- What is being tested?
- VIR-5818 and pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 645 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 13 Apr 2022to Apr 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
12 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
12 sites in 5 countries
Spain7 sites, 7 recruiting
- Recruiting
Investigational site number #255
Barcelona, 08023
- Recruiting
Investigational site number #251
Barcelona, 08035
- Recruiting
Investigational site number #257
Madrid, Madrid, 28034
- Recruiting
Investigational site number #254
Madrid, 28027
- Recruiting
Investigational site number #252
Madrid, 28050
- Recruiting
Investigational site number #250
Pamplona, 31008
- Recruiting
Investigational site number #253
Pozuelo de Alarcón, 28223
Australia2 sites, 1 recruiting
- Active, not recruiting
Investigational site number #100
Melbourne, Victoria, 3000
- Recruiting
Investigational site number #101
Randwick, 2031
United States1 site, 1 recruiting
- Recruiting
City of Hope National Medical Center
Duarte, California, 91010
France1 site, 1 recruiting
- Recruiting
Investigational site number #150
Toulouse, 31059
Portugal1 site, 1 recruiting
- Recruiting
Investigational site number #200
Porto, 4200-072
About this study
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
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.
- Being tested
- VIR-5818, pembrolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VIR-5818Drug
Administered as IV infusion
pembrolizumabDrug
Also called KEYTRUDA®
Administered as IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1 (dose escalation) | Experimental | Participants will receive single-agent VIR-5818 Receives: Drug: VIR-5818 |
| Part 2 (dose escalation) | Experimental | Participants will receive VIR-5818 plus pembrolizumab Receives: Drug: VIR-5818; Drug: pembrolizumab |
| Part 3 (dose expansion) | Experimental | Participants will receive single-agent VIR-5818 Receives: Drug: VIR-5818 |
| Part 4 (dose expansion | Experimental | Participants will receive VIR-5818 plus pembrolizumab Receives: Drug: VIR-5818; Drug: pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicity - Part 1 and Part 2
Measured: 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
Measured: 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.
Measured: 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.
Measured: Up to approximately 55 months
Secondary outcomes (11)
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).
Measured: 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.
Measured: Up to approximately 55 months
Pharmacokinetics (PK) parameter: Area under the concentration-time curve (AUC)
Measured: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Maximum plasma concentration (Cmax)
Measured: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Minimum serum concentration (Cmin)
Measured: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Clearance (CL)
Measured: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Volume of distribution at steady-state (Vss)
Measured: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Accumulation ratio
Measured: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Half-life (t1/2)
Measured: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
Incidence of anti-drug antibodies (ADAs) to VIR-5818
Measured: 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
Measured: Up to approximately 55 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2022
- Study start13 Apr 2022
- Primary completionApr 2028 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced or Metastatic HER2-Expressing CancersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 645 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vir Biotechnology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05356741
- Sponsor's protocol ID
- VIR-5818-V101
- Other IDs
- MK-3475-D14, KEYNOTE-D14
- Status last verified
- Aug 2026
- First submitted
- 26 Apr 2022
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05356741
- Acronym / sponsor ID
- VIR-5818-V101
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 645 participants (estimated)
- Lead sponsor
- Vir Biotechnology, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 13 Apr 2022 (actual)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 2 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1 (dose escalation) | Experimental | Drug: VIR-5818Participants will receive single-agent VIR-5818 |
| Part 2 (dose escalation) | Experimental | Drug: VIR-5818, Drug: pembrolizumabParticipants will receive VIR-5818 plus pembrolizumab |
| Part 3 (dose expansion) | Experimental | Drug: VIR-5818Participants will receive single-agent VIR-5818 |
| Part 4 (dose expansion | Experimental | Drug: VIR-5818, Drug: pembrolizumabParticipants will receive VIR-5818 plus pembrolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VIR-5818Administered as IV infusion | Drug | Part 1 (dose escalation), Part 2 (dose escalation), Part 3 (dose expansion), Part 4 (dose expansion |
| pembrolizumabAlso: KEYTRUDA®Administered as IV infusion | Drug | Part 2 (dose escalation), Part 4 (dose expansion |
Primary outcome
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.
11 secondary outcomes
ORR - Part 3 and Part 4
Time frame: Up to approximately 55 months
DOR - Part 3 and Part 4
Time frame: Up to approximately 55 months
Pharmacokinetics (PK) parameter: Area under the concentration-time curve (AUC)
Time frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Maximum plasma concentration (Cmax)
Time frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Minimum serum concentration (Cmin)
Time frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Clearance (CL)
Time frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Volume of distribution at steady-state (Vss)
Time frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Accumulation ratio
Time frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
PK parameter: Half-life (t1/2)
Time frame: Predose, intermediate timepoints at multiple cycles (1 Cycle = 21 days) up to approximately 55 months
Incidence of anti-drug antibodies (ADAs) to VIR-5818
Time frame: Multiple timepoints at specified cycles (1 Cycle = 21 days) up to approximately 55 months
All parts: Disease control rate (DCR)
Time frame: Up to approximately 55 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing VIR-5818 and pembrolizumab in people with Locally Advanced or Metastatic HER2-Expressing Cancers, run by Vir Biotechnology, Inc. at 12 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Spain, Australia, United States, France, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Inquiry (415-654-5281, clinicaltrials@vir.bio), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicity - Part 1 and Part 2 (time frame: Up to approximately 21 days (Part 1) and 42 days (Part 2)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.