Advanced Cancer, Angiosarcoma, Breast Cancer, Cancer, Colorectal Cancer, Liver Cancer, Locally Advanced Carcinoma, Metastatic Solid Tumor, Pancreatic Cancer, Prostate Cancer, Solid Tumor
Conditions
Keywords
ADC, Antibody Drug Conjugate, AGX101
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.
Interventions
DRUGAGX101
Antibody Drug Conjugate
Sponsors
Angiex, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A mTPI-2 design (Guo et al, 2017) with a target DLT rate of at most 30% will be applied for dose-escalation and expansion to determine the AGX101 RP2D.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 an unresected primary colorectal tumor 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| 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 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). |
| Efficacy as measured by Duration of Treatment | Approximately 6 months and up to 3 years | — |
| Overall Survival | Approximately 6 months and up to 3 years | — |
Countries
United States
Contacts
CONTACTGlen Weiss, MD
STUDY_DIRECTORGlen Weiss, MD
Medical Lead
Outcome results
None listed