Evaluating VIR-5525 and its combination with Pembrolizumab for advanced solid tumors

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

This study is testing a new treatment called VIR-5525, alone and with another drug called pembrolizumab, to see if it can help people with advanced solid tumors that have a specific protein called EGFR.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 450 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vir Biotechnology, Inc. (Industry-sponsored)
• Drugs / interventions: pembrolizumab, radiation
• Locations: 4 sites (Scottsdale, Arizona and 3 other locations)
• Trial ID: NCT06960395 on ClinicalTrials.gov

What this trial studies

This Phase 1 clinical trial aims to assess the safety and preliminary efficacy of VIR-5525, both as a standalone treatment and in combination with pembrolizumab, for patients with locally advanced or metastatic solid tumors that express EGFR. The study is structured into four parts: dose escalation and expansion for VIR-5525 alone, and dose escalation and expansion for the combination therapy. Participants will be closely monitored for safety and anti-tumor activity throughout the trial. The study is designed to provide initial insights into the potential of VIR-5525 in treating these challenging malignancies.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with unresectable, locally advanced, or metastatic solid tumors that are EGFR positive.

Not a fit: Patients with solid tumors that do not express EGFR or those with upper esophageal or salivary gland tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced solid tumors expressing EGFR.

How similar studies have performed: Other studies have shown promise with similar approaches targeting EGFR in solid tumors, indicating potential for success.

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.

OR

• 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.

Where this trial is running

Scottsdale, Arizona and 3 other locations

• Honor Health Research Institute — Scottsdale, Arizona, United States (Recruiting)
• MD Anderson — Houston, Texas, United States (Recruiting)
• Wollongong Hospital — Wollongong, New South Wales, Australia (Recruiting)
• Princess Alexandra Hospital — Woolloongabba, Queensland, Australia (Recruiting)

Study contacts

• Study coordinator: Study Inquiry

Conditions Solid Tumor Malignancies; EGFR Positive Solid Tumors; EGFR; VIR-5525