Solid Tumor Cancer, Locally Advanced, Metastatic Solid Tumors, Lung Cancers, Epithelial Tumor
Conditions
Keywords
Solid Tumors, Metastatic, Locally Advanced, Lung Cancer, Epithelial Solid Tumors
Brief summary
This study, the first clinical trial of AVZO-1418, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of AVZO-1418 when administered intravenously as a monotherapy and potentially in combination therapy to patients with locally advanced or metastatic epithelial solid tumors.
Detailed description
This first-in-human, Phase 1/2 study will aim to obtain safety and tolerability data when AVZO-1418 is administered intravenously to patients with locally advanced or metastatic epithelial solid tumors. Phase 1 is a dose escalation phase which will assess the safety and tolerability of AVZO-1418 and determine the maximum tolerated dose (MTD) and preliminary recommended Phase 2 dose (RP2D) of AVZO-1418 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-1418 as a monotherapy and potentially in combination therapy.
Interventions
DRUGAVZO-1418
Specific dose in protocol specified schedule
Per label based on combination agent used
DRUGCombination Agent 2
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 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Patient must be an adult, between 18 and 75 years of age 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 epithelial 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
* Uncontrolled hypertension. * 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. * 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 a 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 relief (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