EGFR, EGFR Positive Solid Tumors, Solid Tumor Malignancies
Conditions
Keywords
VIR-5525
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
Interventions
DRUGVIR-5525
Pharmaceutical Form: Solution for Infusion Route of Administration: Intravenous (IV) infusion
DRUGPembrolizumab
Pharmaceutical Form: Solution for Infusion Route of Administration: Intravenous (IV) infusion
Sponsors
Vir Biotechnology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Objectives (Parts 1 and 3) | 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 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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 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, area under the curve (AUC), 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. |
Countries
Australia, United States
Contacts
CONTACTStudy Inquiry
STUDY_DIRECTORClinical Sciences & Operations
Vir Biotechnology
Outcome results
None listed