A Study to Evaluate Safety, Tolerability and Preliminary Activity of AGX101 in Participants With Advanced Solid Tumors
Phase 1
Recruiting
- Conditions
- CancerAdvanced CancerLocally Advanced CarcinomaMetastatic Solid TumorBreast CancerProstate CancerColorectal CancerPancreatic CancerLiver CancerAngiosarcoma
- Interventions
- Registration Number
- NCT06440005
- Lead Sponsor
- Angiex, Inc.
- Brief Summary
AGX101 is an antibody-drug conjugate (ADC) therapy for tumor-forming cancers. The purpose of this study is to learn about AGX101 effects and safety at various dose levels in an all-comers advanced solid cancer patient population. AGX101will be administered intravenously.
Dosing of AGX101 will be repeated once every 3, 6 or 9 weeks. Participants may continue study treatment until disease progression, unacceptable toxicity, or consent withdrawal. Subjects will attend an end of treatment visit and will receive two safety follow-up telephone contacts up to 90 days following the last dose of study drug.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
Inclusion Criteria
- Histologically confirmed unresectable, locally advanced, or metastatic solid tumors.
- Refractory to or relapsed after all standard therapies known to provide proven clinical benefit, unless the patient is not a candidate for standard treatment, there is no standard treatment, or the patient refuses standard treatment after expressing an understanding of all available therapies with proven clinical benefit
- Willing to authorize use of existing archival tissue, unless otherwise discussed with Sponsor
- Time since the last dose of prior therapy to treat underlying malignancy (including other investigational therapy): Systemic cytotoxic chemotherapy: ≥ the duration of the most recent cycle of the previous regimen (with a minimum of 2 weeks for all, except 6 weeks for systemic nitrosourea or systemic mitomycin-C); Biologic therapy (eg, antibodies): ≥ 3 weeks; Small molecule therapies: ≥ 5 × half-life
- Have an ECOG performance status of 0 to 1
- Have adequate organ function
- LVEF ≥ 50%, as determined on cardiac ECHO or cardiac multiple-gated acquisition (MUGA) scan
- Highly effective contraception for both male and female patients throughout the study
Exclusion Criteria
- Colorectal cancer patients with unresected colorectal tumors and non-small-cell lung cancer with predominant squamous histology (ie, squamous cell carcinoma of the lung) are excluded unless otherwise discussed and approved by Sponsor
- Clinically unstable central nervous system (CNS) tumors or brain metastasis (stable and/or asymptomatic CNS metastases allowed)
- Have not recovered to ≤ Grade 1 or baseline from all AEs due to previous therapies (patients with ≤ Grade 2 neuropathy, endocrine-related irAEs, or other AEs may be eligible after discussion with the Sponsor)
- Has an active vasculitis that has required systemic treatment in the past 2 years prior to starting study treatment
- Significant (ie, ≥ Grade 2) ocular disturbances
- Variceal bleeding within 6 months prior to treatment, currently untreated or incompletely treated varices with bleeding, or who otherwise are at a high risk of bleeding
- Any other concurrent antineoplastic treatment except for allowed local radiation of lesions for palliation (to be considered non-target lesions after treatment) and hormone ablation
- Uncontrolled or life-threatening symptomatic concomitant disease, including known symptomatic HIV positive with an AIDS defining opportunistic infection within the last year, known symptomatic active hepatitis B or C, or known active tuberculosis
- Has undergone a major surgery within 3 weeks prior to starting study treatment or has inadequate healing or recovery from complications of surgery prior to starting study treatment
- Has received prior radiotherapy within 2 weeks prior to starting study treatment
- Has or had a potentially life-threatening second malignancy requiring systemic treatment within the last 3 years, or which would impede evaluation of treatment response
- Clinically significant cardiovascular disease
- Patients on a potent CYP3A inhibitor or CPY3A inducer who cannot be changed to another medication
- Has an active infection requiring concurrent systemic antibiotic therapy
- A woman of child-bearing potential (WOCBP) who has a positive pregnancy test prior to treatment
- Is breastfeeding or expecting to conceive or father children within the projected duration of the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation Phase AGX101 AGX-101, initial 90-minute IV infusion, second 60-minute IV infusion and 30 minute subsequent IV infusions on Day 1 of every 3, 6 or 9-week cycle in Dose Escalation Phase. Dose escalation will be carried out in sequential cohorts of escalating doses, with an expansion cohort in advanced angiosarcoma. Dose Expansion Phase AGX101 AGX-101, initial 90-minute IV infusion, second 60-minute IV infusion and 30 minute subsequent IV infusions on Day 1 of every every 3, 6 or 9-week cycle in Dose Escalation Phase. Dose expansion will be carried out with a selected dose and selected cancer type.
- Primary Outcome Measures
Name Time Method Number of participants with adverse events Screening through end of treatment, approximately 6 months and up to 3 years Evaluation of the incidence, severity, and duration of adverse events
Acceptable maximum tolerated dose for participants 21 days following the first dose of AGX101 (Day 1 through Day 21) Maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of AGX101 will be characterized
- Secondary Outcome Measures
Name Time Method Terminal elimination half life (PK) 22 days following the first dose of AGX101 (Day 1 through Day 22) Determination of the terminal elimination half-life (t½)
Overall Survival Approximately 6 months and up to 3 years AUC (PK) 22 days following the first dose of AGX101 (Day 1 through Day 22) Determination of the AUC in 1 dosing interval
Cmax (PK) 22 days following the first dose of AGX101 (Day 1 through Day 22) Determination of the Cmax concentration over a dosing interval, systemic clearance, volume of distribution at steady-state (Vss), and accumulation ratio from first dose to steady-state
Efficacy as measured by Duration of Response (DoR) Assessed by Investigator Approximately 6 months and up to 3 years Determination of the duration of response (DoR)
Efficacy as measured by Disease Control Rate (DCR) Approximately 6 months and up to 3 years Determination of the disease control rate (DCR)
Efficacy as measured by Proportion of Participants with Progression Free Survival (PFS) According to RECIST v1.1 Evaluated by the Investigator Approximately 6 months and up to 3 years Determine progression-free survival (PFS)/PFS assessed per immune-related response evaluation criteria (iPFS).
Number of Participants with Antidrug Antibodies (ADA) to AGX101 Approximately 6 months and up to 3 years Incidence and titers of ADA will be measured
Efficacy as measured by Proportion of Participants with Objective Response Rate (ORR) According to RECIST v1.1 Evaluated by the Investigator Approximately 6 months and up to 3 years Determination the objective response rate (ORR)
Efficacy as measured by Duration of Treatment Approximately 6 months and up to 3 years
Trial Locations
- Locations (2)
NEXT Oncology
🇺🇸San Antonio, Texas, United States
Sarah Cannon Research Center
🇺🇸Nashville, Tennessee, United States