Safety and Preliminary Efficacy of VIR-5525 and VIR-5525 + Pembrolizumab in Participants With Locally Advanced or Metastatic Solid Tumors
- 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
- Short title
- 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
- Control arm
- Open label
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Completion date
- 2029-08-01
- First posted
- 2025-05-07
- Registry last updated
- 2026-04-13
- Primary completion date
- 2029-08-01
- Start date
- 2025-07-22
- Participants
- Participant count basis
- Estimated
- Planned participants
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Vir Biotechnology, Inc.
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT06960395
- ClinicalTrials.gov ID
- NCT06960395
- Registry record
- Open registry record
- Allocation
- Not randomised
- Model
- Sequential
- Purpose
- Treatment
- Masking
- No masking
Primary Safety Objectives (Parts 1 and 3)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
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.
Primary Safety Objectives (Parts 1 and 3)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
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.
Primary Efficacy Objectives (Parts 2 and 4)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
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.
Secondary Safety Objectives (Parts 1 and 3)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Objective: To further evaluate the safety and tolerability of VIR-5525 as a monotherapy (Part 2) and in combination with pembrolizumab (Part 4). Endpoint: Incidence and severity of AEs, with severity determined according to NCI CTCAE v5.0, ASTCT CRS, or ASTCT ICANS Consensus Grading, as appropriate.
Secondary Efficacy Objectives (Parts 1 and 3)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Objective: To evaluate the preliminary anti-tumor activity of VIR-5525 as monotherapy (Part 1) and in combination with pembrolizumab (Part 3). Endpoint: Objective response, defined as a CR or PR per RECIST v1.1. Endpoint: DOR, defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, per RECIST v1.1.
Secondary Efficacy Objectives (Parts 2 and 4)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Objective: To further 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 and schedule. Endpoint: DOR, defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, per RECIST v1.1.
Secondary Efficacy Objectives (Parts 2 and 4)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Objective: To further 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 and schedule. Endpoint: PFS (per investigator using RECIST v1.1), defined as the length of time from the start of treatment until first documented disease progression or death.
Secondary PK Objectives (Parts 1 Through 4)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Objective: To characterize the PK profile of VIR-5525 as monotherapy (Parts 1 and 2) and in combination with pembrolizumab (Parts 3 and 4). Endpoint: PK parameters of VIR-5525, including, but not limited to, area under the curve (AUC), calculated as data allow.
Secondary PK Objectives (Parts 1 Through 4)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Objective: To characterize the PK profile of VIR-5525 as monotherapy (Parts 1 and 2) and in combination with pembrolizumab (Parts 3 and 4). Endpoint: PK parameters of VIR-5525, including, but not limited to, maximum concentration of the drug (Cmax), calculated as data allow.
Secondary PK Objectives (Parts 1 Through 4)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Objective: To characterize the PK profile of VIR-5525 as monotherapy (Parts 1 and 2) and in combination with pembrolizumab (Parts 3 and 4). Endpoint: PK parameters of VIR-5525, including, but not limited to, time to peak drug concentration (tmax), calculated as data allow.
Secondary PK Objectives (Parts 1 Through 4)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Objective: To characterize the PK profile of VIR-5525 as monotherapy (Parts 1 and 2) and in combination with pembrolizumab (Parts 3 and 4). Endpoint: PK parameters of VIR-5525, including, but not limited to, drug accumulation ratio (Rac), calculated as data allow.
Secondary Immunogenicity Objectives (Parts 1 Through 4)
Timeframe: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Objective: To evaluate the immunogenicity of VIR-5525 as monotherapy (Parts 1 and 2) and in combination with pembrolizumab (Parts 3 and 4). Endpoint: Incidence of ADAs to VIR-5525 at baseline and incidence of treatment-emergent ADAs to VIR-5525.
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Healthy volunteers
- No
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.
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.
- Honor Health Research InstituteScottsdale, United StatesRecruiting
- MD AndersonHouston, United StatesRecruiting
- Wollongong HospitalWollongong, AustraliaRecruiting
- Princess Alexandra HospitalWoolloongabba, AustraliaRecruiting
- 2023
- 2023-508555-39
- U1111-1294-8156
- AMX-525