Safety, Pharmacokinetics, and Preliminary Efficacy of VIR-5500 (AMX-500) in Prostate Cancer

Vir Biotechnology

Status and phase: Enrolling; Phase 1

Conditions: Hormone-refractory Prostate Cancer

Treatments: Combination Product: ARSI; Drug: VIR-5500

Study type: Interventional

Funder types: Industry

Identifiers

NCT05997615

2023-503495-24 (Registry Identifier)

U1111-1287-6968 (Registry Identifier)

VIR-5500-V101

AMX-500 (Other Identifier)

Details and patient eligibility

About

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)

Full description

Duration of the study up to approximately 48 months.

Enrollment: 437 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Applicable to Parts 1 and 2

1. Have metastatic disease, defined by ≥ 1 metastatic lesion that is present on baseline computed tomography (CT), magnetic resonance imaging (MRI), or bone scan imaging

2. 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
   • Appearance of ≥ 2 new lesions in bone scan

3. Have been treated with ≥ 1 second-generation androgen-signaling inhibitor, including abiraterone, apalutamide, darolutamide, and/or enzalutamide

4. Have been treated with ≥ 1 prior taxane regimens (e.g., docetaxel, cabazitaxel)

5. Are deemed unsuitable for standard of care

Applicable to Part 2, 3a and Part 4a,

1. Have metastatic CRPC, defined by ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging that has documented progressive disease (PD) based on ≥ 1 of the following 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
   • Appearance of ≥2 new lesions in bone scan

2. Participants with metastatic hormone sensitive prostate cancer (mHSPC) or with biochemical recurrent prostate cancer (BRPC) may also participate in select cohorts of this clinical trial.

Exclusion criteria

1. Presence of dominant histopathological features representative of sarcomatoid, spindle cell, or neuroendocrine small cell components
2. Has acute or chronic infections
3. Has a concomitant medical or inflammatory condition that may increase the risk of toxicity to VIR-5500 (AMX-500), per the Investigator
4. Has lesions in proximity of vital organs
5. Has known active CNS metastases and/or carcinomatous meningitis The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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437 participants in 4 patient groups

Part 1: VIR-5500 Monotherapy Dose Escalation

Experimental group

Description:

VIR-5500 will be administered as a monotherapy in patients with mCRPC over a 21-day or 28-day cycle

Treatment:

Drug: VIR-5500

Part 2: VIR-5500 Monotherapy Dose Expansion

Experimental group

Description:

VIR-5500 will be administered as a monotherapy in patients with mCRPC over a 21-day or 28-day cycle

Treatment:

Drug: VIR-5500

Part 3a: VIR-5500 in combination with an ARSI for Dose Escalation

Experimental group

Description:

VIR-5500 will be administered in combination with ARSI over a 21-day or 28-day cycle

Treatment:

Drug: VIR-5500

Combination Product: ARSI

Part 4a: VIR-5500 in combination with an ARSI for Dose Expansion

Experimental group

Description:

VIR-5500 will be administered in combination with ARSI over a 21-day or 28-day cycle

Treatment:

Drug: VIR-5500

Combination Product: ARSI