A Study to Evaluate Safety, Tolerability and Preliminary Activity of AGX101 in Participants With Advanced Solid Tumors

Официальное название

A Phase 1, Open-Label, Dose-Escalation and Expansion Study of AGX101, a TM4SF1 Directed Antibody Drug Conjugate in Patients With Unresectable, Locally Advanced, or Metastatic Solid Tumors

Обзор

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.

Вмешательства

• Препарат AGX101
  Antibody Drug Conjugate

Первичные конечные точки

• Acceptable maximum tolerated dose for participants [Срок оценки: 21 days following the first dose of AGX101 (Day 1 through Day 21)]
• Number of participants with adverse events [Срок оценки: Screening through end of treatment, approximately 6 months and up to 3 years]

Вторичные конечные точки (10)

• Terminal elimination half life (PK) [Срок оценки: 22 days following the first dose of AGX101 (Day 1 through Day 22)]
• AUC (PK) [Срок оценки: 22 days following the first dose of AGX101 (Day 1 through Day 22)]
• Cmax (PK) [Срок оценки: 22 days following the first dose of AGX101 (Day 1 through Day 22)]
• Number of Participants with Antidrug Antibodies (ADA) to AGX101 [Срок оценки: Approximately 6 months and up to 3 years]
• Efficacy as measured by Proportion of Participants with Objective Response Rate (ORR) According to RECIST v1.1 Evaluated by the Investigator [Срок оценки: Approximately 6 months and up to 3 years]
• Efficacy as measured by Duration of Response (DoR) Assessed by Investigator [Срок оценки: Approximately 6 months and up to 3 years]
• Efficacy as measured by Disease Control Rate (DCR) [Срок оценки: Approximately 6 months and up to 3 years]
• Efficacy as measured by Proportion of Participants with Progression Free Survival (PFS) According to RECIST v1.1 Evaluated by the Investigator [Срок оценки: Approximately 6 months and up to 3 years]
• Efficacy as measured by Duration of Treatment [Срок оценки: Approximately 6 months and up to 3 years]
• Overall Survival [Срок оценки: Approximately 6 months and up to 3 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 6 центров

• USC/Norris Comprehensive Cancer Center — Los Angeles
• Florida Cancer Specialist — Sarasota
• Washington University School of Medicine — St Louis
• Sarah Cannon Research Center — Nashville
• NEXT Oncology — San Antonio
• NEXT Oncology — Fairfax

Идентификаторы

NCT: NCT06440005 · AGX101-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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