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Recruiting NCT05356741

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

Phase I / Phase II Interventional Locally Advanced or Metastatic HER2-Expressing Cancers

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: VIR-5818, pembrolizumab.
Who it may be relevant to
Registry conditions: Locally Advanced or Metastatic HER2-Expressing Cancers. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Australia, France, Portugal, Spain
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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

Overview

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.

Interventions

  • Drug VIR-5818
    Administered as IV infusion
  • Drug pembrolizumab
    Administered as IV infusion

Primary outcome measures

  • 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]
  • Duration of Response (DOR) - Part 3 and Part 4 [Time frame: Up to approximately 55 months]
Secondary outcome measures (11)
  • 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]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation
Non-randomized
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

Spain · 6 centers
  • Investigational site number #255 — Barcelona
  • Investigational site number #251 — Barcelona
  • Investigational site number #254 — Madrid
  • Investigational site number #252 — Madrid
  • Investigational site number #250 — Pamplona
  • Investigational site number #253 — Pozuelo de Alarcón
Australia · 2 centers
  • Investigational site number #100 — Melbourne
  • Investigational site number #101 — Randwick
France · 1 center
  • Investigational site number #150 — Toulouse
Portugal · 1 center
  • Investigational site number #200 — Porto

Identifiers

NCT: NCT05356741 · VIR-5818-V101 · MK-3475-D14 · KEYNOTE-D14

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗