Clinical trial NCT06440005: A Study to Evaluate Safety, Tolerability and Preliminary Activity of AGX101 in Participants With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Cancer
Advanced Cancer
Locally Advanced Carcinoma
Metastatic Solid Tumor
Breast Cancer
Prostate Cancer
Colorectal Cancer
Pancreatic Cancer
Liver Cancer
Angiosarcoma
Solid Tumor
Keywords: ADC
Antibody Drug Conjugate
AGX101
Lead sponsor: Angiex, Inc.
Sponsor class: INDUSTRY
First posted: 2024-06-03
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Acceptable maximum tolerated dose for participants
timeFrame: 21 days following the first dose of AGX101 (Day 1 through Day 21)
measure: Number of participants with adverse events
timeFrame: Screening through end of treatment, approximately 6 months and up to 3 years
Secondary outcomes:
measure: Terminal elimination half life (PK)
timeFrame: 22 days following the first dose of AGX101 (Day 1 through Day 22)
measure: AUC (PK)
timeFrame: 22 days following the first dose of AGX101 (Day 1 through Day 22)
measure: Cmax (PK)
timeFrame: 22 days following the first dose of AGX101 (Day 1 through Day 22)
measure: Number of Participants with Antidrug Antibodies (ADA) to AGX101
timeFrame: Approximately 6 months and up to 3 years
measure: Efficacy as measured by Proportion of Participants with Objective Response Rate (ORR) According to RECIST v1.1 Evaluated by the Investigator
timeFrame: Approximately 6 months and up to 3 years
measure: Efficacy as measured by Duration of Response (DoR) Assessed by Investigator
timeFrame: Approximately 6 months and up to 3 years
measure: Efficacy as measured by Disease Control Rate (DCR)
timeFrame: Approximately 6 months and up to 3 years
measure: Efficacy as measured by Proportion of Participants with Progression Free Survival (PFS) According to RECIST v1.1 Evaluated by the Investigator
timeFrame: Approximately 6 months and up to 3 years
measure: Efficacy as measured by Duration of Treatment
timeFrame: Approximately 6 months and up to 3 years
measure: Overall Survival
timeFrame: Approximately 6 months and up to 3 years
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Sarah Cannon Research Center
state: Tennessee
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
Study officials:
affiliation: Medical Lead
name: Glen Weiss, MD
role: STUDY_DIRECTOR
References: