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

Overview

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

Interventions

• Drug VIR-5525
  Pharmaceutical Form: Solution for Infusion Route of Administration: Intravenous (IV) infusion
• Drug Pembrolizumab
  Pharmaceutical Form: Solution for Infusion Route of Administration: Intravenous (IV) infusion

Primary outcome measures

• Primary Safety Objectives (Parts 1 and 3) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]
• Primary Safety Objectives (Parts 1 and 3) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]
• Primary Efficacy Objectives (Parts 2 and 4) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]

Secondary outcome measures (9)

• Secondary Safety Objectives (Parts 1 and 3) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]
• Secondary Efficacy Objectives (Parts 1 and 3) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]
• Secondary Efficacy Objectives (Parts 2 and 4) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]
• Secondary Efficacy Objectives (Parts 2 and 4) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]
• Secondary PK Objectives (Parts 1 Through 4) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]
• Secondary PK Objectives (Parts 1 Through 4) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]
• Secondary PK Objectives (Parts 1 Through 4) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]
• Secondary PK Objectives (Parts 1 Through 4) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]
• Secondary Immunogenicity Objectives (Parts 1 Through 4) [Time frame: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.]

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.

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• Honor Health Research Institute — Scottsdale
• MD Anderson — Houston

Australia · 2 centers

• Wollongong Hospital — Wollongong
• Princess Alexandra Hospital — Woolloongabba

Identifiers

NCT: NCT06960395 · VIR-5525-V101 · U1111-1294-8156 · 2023-508555-39 · AMX-525

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗