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

Cancer Clinical Trial

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 Including Triple-Negative Breast Cancer and Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06440005
• Other study ID #: AGX101-001
• Status: Recruiting
• Phase: Phase 1
• Start date: May 2024
• Est. completion date: May 2027

Study information

• Verified date: May 2024
• Source: Angiex, Inc.
• Contact: Paul Jaminet, PhD
• Phone: 617-576-1753
• Email: clinical[@]angiex.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: May 2027
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed unresectable, locally advanced, or metastatic solid tumors including triple-negative breast cancer (TNBC) and pancreatic ductal adenocarcinoma (PDAC).

• 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 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Cancer
• Breast Neoplasms
• Cancer
• Metastatic Solid Tumor
• Pancreas Cancer
• Pancreatic Adenocarcinoma
• Pancreatic Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• AGX101
Antibody Drug Conjugate

Locations

Country	Name	City	State
United States	Sarah Cannon Research Center	Nashville	Tennessee
United States	NEXT Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Angiex, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acceptable maximum tolerated dose for participants	Maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of AGX101 will be characterized	21 days following the first dose of AGX101 (Day 1 through Day 21)
Primary	Number of participants with adverse events	Evaluation of the incidence, severity, and duration of adverse events	Screening through end of treatment, approximately 6 months and up to 3 years
Secondary	Terminal elimination half life (PK)	Determination of the terminal elimination half-life (t½)	22 days following the first dose of AGX101 (Day 1 through Day 22)
Secondary	AUC (PK)	Determination of the AUC in 1 dosing interval	22 days following the first dose of AGX101 (Day 1 through Day 22)
Secondary	Cmax (PK)	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	22 days following the first dose of AGX101 (Day 1 through Day 22)
Secondary	Number of Participants with Antidrug Antibodies (ADA) to AGX101	Incidence and titers of ADA will be measured	Approximately 6 months and up to 3 years
Secondary	Efficacy as measured by Proportion of Participants with Objective Response Rate (ORR) According to RECIST v1.1 Evaluated by the Investigator	Determination the objective response rate (ORR)	Approximately 6 months and up to 3 years
Secondary	Efficacy as measured by Duration of Response (DoR) Assessed by Investigator	Determination of the duration of response (DoR)	Approximately 6 months and up to 3 years
Secondary	Efficacy as measured by Disease Control Rate (DCR)	Determination of the disease control rate (DCR)	Approximately 6 months and up to 3 years
Secondary	Efficacy as measured by Proportion of Participants with Progression Free Survival (PFS) According to RECIST v1.1 Evaluated by the Investigator	Determine progression-free survival (PFS)/PFS assessed per immune-related response evaluation criteria (iPFS).	Approximately 6 months and up to 3 years
Secondary	Efficacy as measured by Duration of Treatment		Approximately 6 months and up to 3 years
Secondary	Overall Survival		Approximately 6 months and up to 3 years