BEACON-1: Study of AVZO-103 as a Single Agent and in Combination Therapy in Patients With Locally Advanced or Metastatic Urothelial Cancer or Other Solid Tumors (AVZO-103-1001)

Official title

A Phase 1/2, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AVZO-103, a Nectin4/Trop2 ADC, as a Single Agent and in Combination Therapy in Patients With Locally Advanced or Metastatic Urothelial Cancer or Other Solid Tumors

Overview

This study, the first clinical trial of AVZO-103, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of AVZO-103 when administered intravenously as a monotherapy and in combination therapy to patients with locally advanced or metastatic urothelial cancer or other solid tumors.

Detailed description

Phase 1 is a dose escalation phase which will assess the safety and tolerability of AVZO-103 and determine the maximum tolerated dose (MTD) and preliminary recommended Phase 2 dose (RP2D) of AVZO-103 as a monotherapy. This data can guide selection of combination schedules and agents.

Phase 2 is a dose expansion phase that will aim to assess the antitumor activity of AVZO-103 as a monotherapy and in combination therapy.

Interventions

• Drug AVZO-103
  Specific dose in protocol specified schedule
• Drug Combination Agent
  Per label based on combination agent used

Primary outcome measures

• Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1) [Time frame: Approximately 2 years]
• Determine the maximum tolerated dose (MTD) and/or preliminary recommended Phase 2 dose (RP2D) (Phase 1) [Time frame: Approximately 16 months]
• Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1) [Time frame: From baseline until end of study treatment or study completion (approximately 2 years)]
• Objective Response Rate (ORR) (Phase 2) [Time frame: From baseline through disease progression or study completion (approximately 2 years)]

Secondary outcome measures (12)

• Objective Response Rate (ORR) (Phase 1) [Time frame: From baseline through disease progression or study completion (approximately 2 years)]
• Duration of Response (DOR) (Phase 1 and 2) [Time frame: From baseline through disease progression or study completion (approximately 2 years)]
• Disease Control Rate (DCR) (Phase 1 and 2) [Time frame: From baseline through disease progression or study completion (approximately 2 years)]
• Progression Free Survival (PFS) (Phase 1 and 2) [Time frame: From baseline through time to event on study or study completion (approximately 2 years)]
• Overall Survival (OS) (Phase 1 and 2) [Time frame: Approximately 76 months]
• PK Parameters: Maximum observed concentration (Cmax) (Phase 1) [Time frame: Up to 2 years]
• PK Parameters: Minimum observed concentration (Cmin) (Phase 1) [Time frame: Up to 2 years]
• PK Parameters: Time to maximum observed concentration (Tmax) (Phase 1) [Time frame: Up to 2 years]
• PK Parameters: Elimination half-life (T1/2) (Phase 1) [Time frame: Up to 2 years]
• PK Parameters: Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) (Phase 1) [Time frame: Up to 2 years]
• PK Parameters: Area under the concentration-time curve from time 0 to infinity (AUCinf) (Phase 1) [Time frame: Up to 2 years]
• PK Parameters: Area under the concentration-time curve from time 0 to the end of the dosing period (AUCτ) (Phase 1) [Time frame: Up to 2 years]

Eligibility criteria

Inclusion criteria

• Patient must be an adult, 18 years of age and older with an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 and a life expectancy of > 3 months.
• Patients with histologically or cytologically confirmed locally advanced/metastatic malignancies for tumor types of preferred indications:

o Locally advanced or metastatic urothelial cancer and other solid tumors (as specified in the protocol).

• Measurable disease as assessed by Investigator using RECIST v1.1.
• Agree to provide molecular test report results to confirm eligibility and archival tumor samples and/or fresh biopsy, as applicable.
• Other protocol-defined Inclusion criteria apply.

Exclusion criteria

• Patients with active central nervous system (CNS) metastases are not eligible. Patients with asymptomatic and treated brain metastases may participate if they are radiologically stable for at least 4 weeks prior to the first dose of this study and do not require steroid treatment. Patients with suspected or confirmed leptomeningeal disease are not eligible, even if treated.
• Prior Stevens-Johnson syndrome/toxic epidermal necrolysis.
• History of drug-induced interstitial lung disease (ILD).
• History of any serious cardiovascular condition.
• Infection requiring IV antibiotics, antivirals, or antifungals within 2 weeks prior to first dose.
• History of allogenic stem cell or solid organ transplant.
• Other protocol-defined Exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 13 centers

• Avenzo Therapeutics Recruiting Site — San Francisco
• Avenzo Therapeutics Recruiting Site — Aurora
• Avenzo Therapeutics Recruiting Site — New Haven
• Avenzo Therapeutics Recruiting Site — Orlando
• Avenzo Therapeutics Recruiting Site — Tampa
• Avenzo Therapeutics Recruiting Site — Boston
• Avenzo Therapeutics Recruiting Site — New York
• Avenzo Therapeutics Recruiting Site — Chapel Hill
• … and 5 more centers

Identifiers

NCT: NCT07193511 · AVZO-103-1001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗