Clinical trial NCT06960395: Safety and Preliminary Efficacy of VIR-5525 and VIR-5525 + Pembrolizumab in Participants With Locally Advanced or Metastatic Solid Tumors
Official title: A Phase 1, First-in-Human Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of VIR-5525 Alone and in Combination With Pembrolizumab in Participants With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor Malignancies
EGFR Positive Solid Tumors
EGFR
Keywords: VIR-5525
Lead sponsor: Vir Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2025-05-07
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

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.

Exclusion Criteria:

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.

The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Primary outcomes:
measure: Primary Safety Objectives (Parts 1 and 3)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
measure: Primary Safety Objectives (Parts 1 and 3)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
measure: Primary Efficacy Objectives (Parts 2 and 4)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Secondary outcomes:
measure: Secondary Safety Objectives (Parts 1 and 3)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
measure: Secondary Efficacy Objectives (Parts 1 and 3)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
measure: Secondary Efficacy Objectives (Parts 2 and 4)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
measure: Secondary Efficacy Objectives (Parts 2 and 4)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
measure: Secondary PK Objectives (Parts 1 Through 4)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
measure: Secondary PK Objectives (Parts 1 Through 4)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
measure: Secondary PK Objectives (Parts 1 Through 4)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
measure: Secondary PK Objectives (Parts 1 Through 4)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
measure: Secondary Immunogenicity Objectives (Parts 1 Through 4)
timeFrame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
Study officials:
affiliation: Vir Biotechnology
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: