Locally Advanced, Metastatic Solid Tumors, Solid Tumor Cancer, Urothelial Cancer
Conditions
Keywords
Solid Tumors, Metastatic, Locally Advanced, Urothelial Cancer
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.
Interventions
DRUGAVZO-103
Specific dose in protocol specified schedule
DRUGCombination Agent
Per label based on combination agent used
Sponsors
Avenzo Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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) | — |
Countries
United States
Contacts
CONTACTMedical Information
Outcome results
None listed