safety and preliminary efficacy of vir-5525 and vir-5525 + pembrolizumab in participants with locally advanced or metastatic solid tumors

Conditions: Solid Tumor Malignancies; EGFR Positive Solid Tumors; EGFR

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


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. * 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.

Keywords: vir-5525