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

A Phase 1, First-in-Human Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of VIR-5500 (AMX-500) in Participants With Prostate Cancer

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)

Study Overview

• Status: Recruiting
• Conditions: Hormone-refractory Prostate Cancer
• Intervention / Treatment: Drug: VIR-5500; Combination product: ARSI

Detailed Description

Duration of the study up to approximately 48 months.

• Study Type: Interventional
• Enrollment (Estimated): 437
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Inquiry; Phone Number: 415-654-5281; Email: clinicaltrials@vir.bio

Study Locations

• Australia
  • Melbourne, Australia, 3000
    • Recruiting
    • Investigational Site Number: 100
  • Sydney, Australia, 2010
    • Recruiting
    • Investigational Site Number: 101
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Investigational Site Number: 250
  • Barcelona, Spain, 08023
    • Withdrawn
    • Investigational Site Number: 251
  • Madrid, Spain, 28223
    • Recruiting
    • Investigational Site Number: 252
  • Madrid, Spain, 28027
    • Recruiting
    • Investigational Site Number: 254
  • Pamplona, Spain, 31008
    • Recruiting
    • Investigational Site Number: 253
• United Kingdom
  • London, United Kingdom, SM2 5PT
    • Recruiting
    • Investigational Site Number: 300
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Investigational Site Number: 403
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Investigational Site Number: 401
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Investigational Site number: 404
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Investigational Site Number: 400

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: VIR-5500 Monotherapy Dose Escalation; VIR-5500 will be administered as a monotherapy in patients with mCRPC over a 21-day or 28-day cycle	Drug: VIR-5500; Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV) infusion
Experimental: Part 2: VIR-5500 Monotherapy Dose Expansion; VIR-5500 will be administered as a monotherapy in patients with mCRPC over a 21-day or 28-day cycle	Drug: VIR-5500; Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV) infusion
Experimental: Part 3a: VIR-5500 in combination with an ARSI for Dose Escalation; VIR-5500 will be administered in combination with ARSI over a 21-day or 28-day cycle	Drug: VIR-5500; Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV) infusion; Combination product: ARSI; Oral administration
Experimental: Part 4a: VIR-5500 in combination with an ARSI for Dose Expansion; VIR-5500 will be administered in combination with ARSI over a 21-day or 28-day cycle	Drug: VIR-5500; Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV) infusion; Combination product: ARSI; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and 3a: Number of participants with treatment-emergent Adverse Events (AEs)	Incidence and severity of AEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months
Part 1 and 3a: Incidence of Dose Limiting Toxicities (DLTs)	Incidence and nature of DLTs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to Day 21 or Day 28
Part 2 and 4a: Prostate-Specific Antigen (PSA) response rate		from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months
Part 2 and 4a: Objective Response Rate (ORR)		from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Part 2 and 4a: Number of participants with Adverse Events (AEs)	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months
Part 1 and 3a: PSA response rate	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months
Part 1 and 3a: Objective Response Rate (ORR)	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months
All parts: Duration of response (DoR)	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months
All parts: Progression Free Survival PFS	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months
All parts: Assessment of PK parameters: Cmax	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months
All parts: Assessment of PK parameters: AUC	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months
All parts: Assessment of PK parameters: Tmax	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months
All parts: Incidence of baseline anti-drug antibodies (ADAs) to VIR-5500	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months
All parts: Incidence of treatment emergent anti-drug antibodies (ADAs) to VIR-5500	from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months

Collaborators and Investigators

• Sponsor: Vir Biotechnology, Inc.
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Estimated): September 29, 2027
• Study Completion (Estimated): September 29, 2027

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: August 11, 2023
• First Posted (Actual): August 18, 2023

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Prostate Cancer; Castration Resistant Prostatic Cancer; High-Risk Biochemical Recurrent Prostate Cancer; Metastatic Castration-resistant Prostate Cancer (mCRPC); Hormone Sensitive Prostate Cancer (HSPC)
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; darolutamide; enzalutamide
• Other Study ID Numbers: VIR-5500-V101; U1111-1287-6968 (Registry Identifier: ICTRP); 2023-503495-24 (Registry Identifier: CTIS); AMX-500 (Other Identifier: Vir Biotechnology, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No