Safety and Preliminary Efficacy of VIR-5525 and VIR-5525 + Pembrolizumab in Participants With Locally Advanced or Metastatic Solid Tumors
- Conditions
- Solid Tumor MalignanciesEGFR Positive Solid TumorsEGFR
- Interventions
- Registration Number
- NCT06960395
- Lead Sponsor
- Vir Biotechnology, Inc.
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 450
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: VIR-5525 Monotherapy Dose Escalation VIR-5525 Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in monotherapy. Part 2: VIR-5525 Monotherapy Dose Expansion VIR-5525 Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in monotherapy. Part 3: VIR-5525 Combination Dose Escalation VIR-5525 Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab. Part 3: VIR-5525 Combination Dose Escalation Pembrolizumab Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab. Part 4: VIR-5525 Combination Dose Expansion VIR-5525 Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab. Part 4: VIR-5525 Combination Dose Expansion Pembrolizumab Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab.
- Primary Outcome Measures
Name Time Method Primary Safety Objectives (Parts 1 and 3) 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) 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 Outcome Measures
Name Time Method Secondary Safety Objectives (Parts 1 and 3) 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) 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) 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) 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) 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.
Trial Locations
- Locations (3)
Honor Health Research Institute
🇺🇸Scottsdale, Arizona, United States
Wollongong Hospital
🇦🇺Wollongong, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia