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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

Not Applicable
Not yet recruiting
Conditions
Solid Tumor Cancer
Locally Advanced
Metastatic Solid Tumors
Urothelial Cancer
Interventions
Drug: AVZO-103
Drug: Combination Agent
Registration Number
NCT07193511
Lead Sponsor
Avenzo Therapeutics, Inc.
Brief Summary

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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
355
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.

Key

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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Phase 1, monotherapyAVZO-103Part A
Phase 1, combinationAVZO-103Part B
Phase 1, combinationCombination AgentPart B
Phase 2, monotherapyAVZO-103Part A
Phase 2, combinationAVZO-103Part B
Phase 2, combinationCombination AgentPart B
Primary Outcome Measures
NameTimeMethod
Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1)Approximately 2 years

Number of participants with DLTs assessed for severity using CTCAE v5.0 criteria will be summarized by dose level.

Determine the maximum tolerated dose (MTD) and/or preliminary recommended Phase 2 dose (RP2D) (Phase 1)Approximately 16 months
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1)From baseline until end of study treatment or study completion (approximately 2 years)
Objective Response Rate (ORR) (Phase 2)From baseline through disease progression or study completion (approximately 2 years)

Defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1.

Secondary Outcome Measures
NameTimeMethod
Objective Response Rate (ORR) (Phase 1)From baseline through disease progression or study completion (approximately 2 years)
Duration of Response (DOR) (Phase 1 and 2)From baseline through disease progression or study completion (approximately 2 years)

Defined as the time from the first confirmed response to radiologic/objective progression.

Disease Control Rate (DCR) (Phase 1 and 2)From baseline through disease progression or study completion (approximately 2 years)

Defined as the proportion of patients who achieve tumor response (CR or PR) and stable disease (SD) after treatment; calculated as the sum of CR, PR, and SD.

Progression Free Survival (PFS) (Phase 1 and 2)From baseline through time to event on study or study completion (approximately 2 years)

Defined as the time from study drug treatment to death or disease progression, as determined by the investigator by radiographic disease assessment according to RECIST v1.1.

Overall Survival (OS) (Phase 1 and 2)Approximately 76 months

Defined as the time from study drug treatment initiation to death from any cause.

PK Parameters: Maximum observed concentration (Cmax) (Phase 1)Up to 2 years
PK Parameters: Minimum observed concentration (Cmin) (Phase 1)Up to 2 years
PK Parameters: Time to maximum observed concentration (Tmax) (Phase 1)Up to 2 years
PK Parameters: Elimination half-life (T1/2) (Phase 1)Up to 2 years
PK Parameters: Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) (Phase 1)Up to 2 years
PK Parameters: Area under the concentration-time curve from time 0 to infinity (AUCinf) (Phase 1)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)Up to 2 years
Determination of RP2D (Phase 2)Approximately 16 months
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 2)From baseline until end of study treatment or study completion (approximately 2 years)
PK Parameters: Apparent Clearance (CL/F) (Phase 1)Up to 2 years
PK Parameters: Apparent volume of distribution at steady-state (Vss) (Phase 1)Up to 2 years
PK Parameters: Accumulation ratio (AR) (Phase 1)Up to 2 years

Trial Locations

Locations (1)

Avenzo Therapeutics Recruiting Site

🇺🇸

Austin, Texas, United States

Avenzo Therapeutics Recruiting Site
🇺🇸Austin, Texas, United States

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