Safety and Preliminary Efficacy of VIR-5525 and VIR-5525 + Pembrolizumab in Participants With Locally Advanced or Metastatic Solid Tumors

NCT06960395 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: VIR-5525-V101U1111-1294-81562023-508555-39AMX-525
• Study Type: interventional
• Target: 450
• Locations: 2 countries
• Sites: 4

Brief Summary

This Phase 1, first-in-human (FIH), dose-escalation and dose-expansion study is designed to evaluate the safety, PK, and preliminary anti-tumor activity of VIR-5525 as a monotherapy and in combination with pembrolizumab in participants with solid tumors that are known to express EGFR. The study will be conducted in the following 4 parts:

• Part 1: VIR-5525 monotherapy dose escalation
• Part 2: VIR-5525 monotherapy dose expansion
• Part 3: VIR-5525 plus pembrolizumab dose escalation
• Part 4: VIR-5525 plus pembrolizumab dose expansion

Conditions

EGFR Positive Solid Tumors; Solid Tumor Malignancies; EGFR

Keywords

VIR-5525

Outcome Measures

Primary Outcomes (3)

• Primary Safety Objectives (Parts 1 and 3)

  Objective: To evaluate the safety and tolerability of escalating doses of VIR-5525 as monotherapy (Part 1) and in combination with pembrolizumab (Part 3). Endpoint: Incidence and severity of AEs, including DLTs, with severity determined according to NCI CTCAE v5.0, ASTCT CRS, or ASTCT ICANS Consensus Grading, as appropriate.

  From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.

• Primary Safety Objectives (Parts 1 and 3)

  Objective: To determine the recommended dose(s) for expansion cohorts of VIR-5525 as monotherapy (Part 1) and in combination with pembrolizumab (Part 3). Endpoint: Incidence and severity of AEs, including DLTs, with severity determined according to NCI CTCAE v5.0, ASTCT CRS, or ASTCT ICANS Consensus Grading, as appropriate.

  From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.

• Primary Efficacy Objectives (Parts 2 and 4)

  Objective: To evaluate the preliminary anti-tumor activity of VIR-5525 as monotherapy (Part 2) and in combination with pembrolizumab (Part 4) at the recommended dose(s) for expansion cohorts. Endpoint: Objective response, defined as a CR or PR per RECIST v1.1.

  From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.

Secondary Outcomes (9)

• Secondary Safety Objectives (Parts 1 and 3)

  From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.

• Secondary Efficacy Objectives (Parts 1 and 3)

  From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.

• Secondary Efficacy Objectives (Parts 2 and 4)

  From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.

• Secondary Efficacy Objectives (Parts 2 and 4)

  From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.

• Secondary PK Objectives (Parts 1 Through 4)

  From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.

Study Arms (4)

Part 1: VIR-5525 Monotherapy Dose Escalation

EXPERIMENTAL

Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in monotherapy.

Drug: VIR-5525

Part 2: VIR-5525 Monotherapy Dose Expansion

EXPERIMENTAL

Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in monotherapy.

Drug: VIR-5525

Part 3: VIR-5525 Combination Dose Escalation

EXPERIMENTAL

Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab.

Drug: VIR-5525; Drug: Pembrolizumab

Part 4: VIR-5525 Combination Dose Expansion

EXPERIMENTAL

Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab.

Drug: VIR-5525; Drug: Pembrolizumab

Interventions

VIR-5525 DRUG

Pharmaceutical Form: Solution for Infusion Route of Administration: Intravenous (IV) infusion

Also known as: AMX-525

Part 1: VIR-5525 Monotherapy Dose Escalation; Part 2: VIR-5525 Monotherapy Dose Expansion; Part 3: VIR-5525 Combination Dose Escalation; Part 4: VIR-5525 Combination Dose Expansion

Pembrolizumab DRUG

Pharmaceutical Form: Solution for Infusion Route of Administration: Intravenous (IV) infusion

Part 3: VIR-5525 Combination Dose Escalation; Part 4: VIR-5525 Combination Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I 01. Are ≥ 18 years of age, or at the country's legal age of majority of the legal adult age is \>18 years, at the time of signing the ICF.
• I 02. Have an ECOG performance status of 0 to 1.
• I 03. Have a life expectancy of at least 12 weeks.
• I 04. Have histological, pathological, or cytological confirmation of disease type that is unresectable, locally advanced, or metastatic.
• I 05. Have measurable disease per RECIST v1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• I 06. Have diseases under study, lines of therapy, and biomarker status, as follows:
• Have one of the following:
• (Parts 1 and 3): NSCLC (nonsquamous or squamous histology), CRC, HNSCC, or CSCC.
• Note: Participants with nasopharyngeal tumors are eligible. Note: Participants with upper esophageal or salivary gland tumors are not eligible.
• Have a solid tumor with EGFR amplification (as previously determined locally with an analytically validated assay in a certified testing laboratory).
• Have no available standard systemic therapy; or standard therapy is intolerable, not effective, or not accessible; or participant has refused standard therapy.

You may not qualify if:

• E 01. Are a WOCBP with a positive serum or urine pregnancy test within 72 hours prior to treatment.
• E 02. Have acute or chronic infections, including the following:
• Acute or chronic active Epstein-Barr virus (EBV) infection (Exception: asymptomatic EBV-positive participants are still eligible)
• Chronic active EBV disease defined as a chronic illness lasting at least 6 months, an increased EBV level in either the tissue or the blood, and lack of evidence of a known underlying immunodeficiency
• History of hepatitis B infection (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (HCV) infection (defined as HCV \[HCV RNA; qualitative\] is detected)
• History of HIV infection. No HIV testing is required unless mandated by the local health authority.
• Active infection requiring systemic therapy within 14 days of Cycle 1 Day 1
• Known positive COVID-19 test result at screening (Exception: If follow-up test is negative, participants may be eligible if asymptomatic and upon consultation with medical monitor)
• E 03. Have a concomitant medical or inflammatory condition that may increase the risk of toxicity to VIR-5525 or pembrolizumab, per the investigator
• E 04. Have a QT interval corrected by Fridericia's method (QTcF) that is \>480 ms
• E 05. Have received prior systemic anti-cancer therapy, including investigational agents, within 5 half-lives prior to first dose of study intervention. For drugs with a long t1/2, such as mAbs, or for drugs for which the t1/2 is not known, the last dose should not have been within 28 days prior to first dose of study intervention.
• Note: If the participant has had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
• E 06. Have received prior radiotherapy within 2 weeks of start of study intervention Note: Participants must have recovered from all radiation-related toxicities to Grade ≤1 or baseline, must not require corticosteroids, and must not have had radiation pneumonitis.
• Exception: External beam radiotherapy, including palliative external radiation, is allowed.
• A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

Sponsors & Collaborators

• Vir Biotechnology, Inc.: lead

Study Sites (4)

Honor Health Research Institute

Scottsdale, Arizona, 85258-4566, United States

RECRUITING

MD Anderson

Houston, Texas, 77030, United States

RECRUITING

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

RECRUITING

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Clinical Sciences & Operations

  Vir Biotechnology

  STUDY DIRECTOR

Central Study Contacts

Study Inquiry

CONTACT

1-415-654-5281; 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 21, 2025
• First Posted: May 7, 2025
• Study Start: July 22, 2025
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); AU (2)