The study will be conducted in 4 parts and will commence with dose escalation of VIR-5500 as a monotherapy (Part 1), followed by combination escalation (Part 3a), monotherapy dose expansion (Part 2) and combination dose expansion (Part 4a).
* Part 1 (Monotherapy Dose Escalation): Single-agent VIR-5500 dose escalation * Part 2 (Monotherapy Dose Expansion): Single-agent VIR-5500 dose expansion * Part 3 (Combination Dose Escalation): VIR-5500 plus another therapeutic agent dose escalation Part 3a (Combination Dose Escalation): VIR-5500 in combination with an androgen receptor signaling inhibitor (ARSI) * Part 4 (Combination Dose Expansion): VIR-5500 plus another therapeutic agent dose expansion Part 4a (Combination Dose Expansion): VIR-5500 in combination with an androgen receptor signaling inhibitor (ARSI)
Have metastatic disease, defined by ≥ 1 metastatic lesion that is present on baseline computed tomography (CT), magnetic resonance imaging (MRI), or bone scan imaging
Have documented progressive mCRPC based on ≥ 1 of the criteria (per PCWG3)
PSA level ≥ 1 ng/mL that has increased on ≥ 2 successive occasions ≥ 1 week apart
Nodal or visceral progression as defined by RECIST v1.1 with PCWG3 modifications
Presence of dominant histopathological features representative of sarcomatoid, spindle cell, or neuroendocrine small cell components
Has acute or chronic infections
Has a concomitant medical or inflammatory condition that may increase the risk of toxicity to VIR-5500 (AMX-500), per the Investigator
Has lesions in proximity of vital organs