AGX101 for Cancer

Recruiting at 2 trial locations

Overseen By Glen Weiss, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Angiex, Inc.

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Colorectal cancer, CNS tumors, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

80 Participants Needed

Trial Summary

Do I need to stop my current medications for the AGX101 trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on a potent CYP3A inhibitor or inducer and cannot switch to another medication. There are also specific time requirements since your last cancer treatment, such as a minimum of 2 weeks for most chemotherapy and 3 weeks for biologic therapy.

What is known about the safety of AGX101 for cancer treatment?

The safety of anti-PD-1 therapies, which include drugs like nivolumab and pembrolizumab, has been studied, showing they are generally better tolerated than traditional treatments, though they can still cause mild to severe side effects. These side effects are often related to the immune system and can affect the skin, lungs, and nervous system, but most are manageable. Long-term safety is still being studied, and there is a need for better ways to manage these side effects. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Glen Weiss, MD

Principal Investigator

Medical Lead

Eligibility Criteria

This trial is for individuals with advanced solid tumors, such as various types of breast cancer and pancreatic cancer. Participants should have a tumor that has not responded to standard treatments or has returned after treatment.

Inclusion Criteria

LVEF ≥ 50%, as determined on cardiac ECHO or cardiac multiple-gated acquisition (MUGA) scan

My organs are working well.

Willing to authorize use of existing archival tissue, unless otherwise discussed with Sponsor

Exclusion Criteria

I haven't had a severe cancer needing treatment in the last 3 years.

I have a serious heart condition.

I am currently taking antibiotics for an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

AGX-101 is administered in escalating doses to determine the maximum tolerated dose

21 days

Visits on Day 1 of every 3, 6, or 9-week cycle

Dose Expansion

AGX-101 is administered at a selected dose to a specific cancer type

Approximately 6 months and up to 3 years

Visits on Day 1 of every 3, 6, or 9-week cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days following the last dose

End of treatment visit and two safety follow-up telephone contacts

Treatment Details

Interventions

• AGX101

Trial Overview AGX101, an antibody-drug conjugate (ADC) designed to target and kill cancer cells, is being tested. Patients will receive AGX101 through an IV every three weeks until their disease progresses, they experience severe side effects, or choose to leave the study.

Participant Groups

Group I: Dose Expansion Phase Experimental Treatment 1 Intervention

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.

Group II: Dose Escalation Phase Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Angiex, Inc.

Lead Sponsor

Trials

1

Recruited

80+

Findings from Research

This study aims to create a comprehensive toxicity profile for anti-PD-1 and anti-PD-L1 drugs by analyzing systematic reviews and meta-analyses, focusing on treatment-related adverse events in cancer patients.

The research will utilize a network meta-analysis approach to synthesize data from various studies, ensuring a thorough understanding of the safety and adverse effects associated with these immunotherapy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 and anti-PD-L1 drugs treatment-related adverse events for patients with cancer: Protocol for an overview of systematic reviews with meta-analyses. Li, J., Liu, M., Wang, J., et al.[2023]

Immunotherapies, particularly anti-PD-1 checkpoint inhibitors like nivolumab and pembrolizumab, have significantly improved survival rates for metastatic melanoma patients while being less toxic than traditional treatments.

Despite their better tolerability, anti-PD-1 therapies can still cause a range of immune-related adverse events, most of which are mild, but there is a pressing need to understand and manage severe side effects due to the increased life expectancy of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of anti PD-1 therapeutics for the treatment of melanoma. Ramelyte, E., Schindler, SA., Dummer, R.[2018]

Targeted therapies for non-small cell lung cancer (NSCLC) have significantly improved treatment options, but their effectiveness can be compromised by issues like poor patient adherence and adverse events.

The review highlights the need for standardized monitoring protocols for the various toxicities associated with these therapies, which can include skin, gastrointestinal, lung, and heart-related side effects, to ensure better patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. Hines, JB., Bowar, B., Levine, E., et al.[2023]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.

While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. Luo, W., Wang, Z., Tian, P., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Anti-PD-1 and anti-PD-L1 drugs treatment-related adverse events for patients with cancer: Protocol for an overview of systematic reviews with meta-analyses. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The safety of anti PD-1 therapeutics for the treatment of melanoma. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. [2023]

4. India pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. [2021]