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.
