NCT05687682

Safety of AM-928 Infusion in Advanced Solid Tumors

A Phase I, Open-Label, Dose-Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AM-928 Infusion in Subjects With Advanced Solid Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: AcadeMab Biomedical Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase I, open-label, dose-escalation study for a novel cancer treatment, AM-928, intravenous infusion antibody for advanced solid tumor. The study is aimed to learn the safety, tolerability, pharmacokinetics, and preliminary efficacy profile of AM-928. The dose escalation strategy will adopt accelerated titration combined with a Bayesian optimal interval (BOIN) design. Seven dose levels are designed and each participant will be assigned to a specific dose regimen depending on the time of enrollment. In the study, each participant will receive AM-928 treatment cycles till meeting any treatment discontinuation criterion and be followed for safety and long-term survival. The whole study is expected to take approximately three years to complete.

Detailed description

This is a first-in-human Phase I, open-label, dose-escalation study to investigate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of AM-928 infusion in subjects with advanced solid tumors in multiple sites in Taiwan. Eligible subjects will be dosed with different dosages of AM-928 in 1 of the 7 dose levels (0.1, 0.3, 1, 3, 6, 10, 15 mg/kg). Dose levels will be escalated from dose Level 1 at 0.3 mg/kg to Level 6 at 15 mg/kg of AM-928 (or may be de-escalated to Level -1 at 0.1 mg/kg), which will be administered (intravenous infusion) once weekly (QW) for 4 weeks (D1, D8, D15, D22) as a treatment cycle until any treatment discontinuation criterion is met. Basically, there will be no breaks between dosing cycles. From Cycle 4, intra-subject dose escalation may be applied if supported by preliminary safety and PK data. The dose escalation strategy will adopt accelerated titration combined with a Bayesian optimal interval (BOIN) design. The accelerated titration will be adopted for 0.3 mg/kg, while the BOIN design will be adopted for other dose levels, including 1 mg/kg, 3 mg/kg, 6 mg/kg, 10 mg/kg, and 15 mg/kg. In the "accelerated titration" stage, if any ≥ Grade 2 adverse event occurs, the current and subsequent dose groups will be changed to the BOIN dose escalation method. The target toxicity rate for the maximum tolerated dose (MTD) is ϕ= 0.3, and the maximum sample size is determined to be 30, maximum of 9 subjects per dose level. A cohort size of 3 and a maximum cohort number of 3 for each dose level will be adopted for subject recruitment. The dose escalation may end when one of the following criteria is met: (1) The planned sample size of 30 has been reached; (2) 9 subjects have been treated and evaluable for DLT at the next intended dose level (should not exceed 9 subjects at one dose level); (3) all doses explored appear to be overly toxic, and the MTD cannot be determined. The Scientific Review Committee (SRC) will review the safety and/or efficacy data at the end of each dose level cohort for escalation or de-escalation decision (when the DLT rate indicates staying at the current dose, the review process may be waived). Besides, an emergency meeting will be held if the SRC has any safety concerns. A final review process is scheduled at the end of dose escalation for MTD determination. The dose with the toxicity rate closest to the target toxicity rate (ϕ= 0.3) will be selected as MTD. If the SRC determines that the safety profile of a specific dose level is unfavorable for subjects, the SRC may eliminate that dose level even if the toxicity rate is below 0.3. In this case, the subsequent subjects will be enrolled into the lower dose level(s) following the BOIN design and the lower dose level with the toxicity rate closest to the target toxicity rate (ϕ= 0.3) will be selected as MTD.

Conditions

• Advanced Solid Tumor

Interventions

Type	Name	Description
BIOLOGICAL	AM-928	AM-928, which is a humanized anti-EpCAM monoclonal antibody developed by AcadeMab Biomedical Inc.

Timeline

• Start date: 2023-07-14
• Primary completion: 2025-06-01
• Completion: 2026-06-01
• First posted: 2023-01-18
• Last updated: 2025-06-18

Locations

1 site across 1 country: Taiwan

Regulatory

• FDA-regulated drug study