Study of the CD40 Agonistic Monoclonal Antibody APX005M

Phase 1

Completed

• Conditions: Cancer; Urothelial Carcinoma; Head and Neck Cancer; NSCLC; MSI-H; Melanoma
• Interventions: Drug: APX005M

• Registration Number: NCT02482168
• Lead Sponsor: Apexigen America, Inc.

Brief Summary

This study is a phase 1 open-label dose escalation study of the immuno-activating monoclonal antibody APX005M in adults with solid tumors. Study is intended to establish the maximum tolerated dose and the overall safety and tolerability of APX005M in 3 different administration schedules.

Detailed Description

APX005M-001 is an open-label study and comprises a dose-escalation portion of approximately 8 dose level cohorts, plus an expansion cohort.

Eligible subjects with solid tumors will receive intravenous APX005M every 3 week, every 2 week or every 1 week until disease progression, unacceptable toxicity or death, whichever occurs first.

Study objectives include:

* Evaluate safety of APX005M

* Determine the maximum tolerated dose of APX005M

* Determine the pharmacokinetic parameters of APX005M: the maximal drug concentration (Cmax), area under the curve of serum concentration over time (Area Under the Curve/ AUC), and half-life (t½).

* Preliminary assessment of clinical response

Study Timeline

• Study Start: 2015-05
• Study First Submitted: 2015-06-11
• Study First Submitted QC: 2015-06-23
• Study First Posted: 2015-06-26
• Primary Completion: 2018-06-13
• Study Completion: 2018-06-19
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-19
• Last Update Posted: 2023-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

• Histologically documented diagnosis of solid tumor
• For subjects in the every 2 week and every 1 week dosing cohorts histologically or cytologically documented diagnosis of urothelial carcinoma, melanoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer, or any solid tumor with high microsatellite instability status (MSI-high)
• No known effective therapy options are available
• Measurable disease by RECIST 1.1
• ECOG performance status of 0 or 1
• Adequate bone marrow, liver and kidney function
• No toxicities related to prior treatment related toxicities with the exception of alopecia and neuropathy
• Negative pregnancy test for women of child bearing potential

Key

Exclusion Criteria

• Any history of or current hematologic malignancy
• Major surgery or treatment with any other investigational agent within 4 weeks
• Uncontrolled diabetes or hypertension
• History of arterial thromboembolic event
• History of congestive heart failure, symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction
• Active known clinically serious infections

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
APX005M every 3 week	APX005M	Subjects receive APX005M intravenously every 3 week until disease progression, unacceptable toxicity or death.
APX005M every 1 week	APX005M	Subjects receive APX005M intravenously every 1 week until disease progression, unacceptable toxicity or death.
APX005M every 2 week	APX005M	Subjects receive APX005M intravenously every 2 week until disease progression, unacceptable toxicity or death.

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicities	Up to 28 days following first dose of APX005M	The rate of DLTs will be assessed in approximately 56 subjects. DLTs will include Grade 4 neutropenia, anemia, thrombocytopenia, Grade 3or 4 nausea, cytokine release syndrome and other Grade 3 non-hematological toxicity
Incidence of adverse events	Through up to approximately 4 weeks following last dose of APX005M	Incidence and severity of AEs and specific laboratory abnormalities graded according to NCI-CTCAE, v4.03

Secondary Outcome Measures

Name	Time	Method
Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST)	Every 8 weeks up to approximately 1 year following first dose of APX005M	Efficacy assessments will follow RECIST 1.1.
Blood concentrations of APX005M	Predose, 0.5, 1, 2, 4, 24, 48 and 168 hours following first and third dose of APX005M	PK parameters of APX005M
Presence and titer of anti-APX005M antibodies	Prior to first dose, approximately 3, 6 and 9 weeks following first dose and approximately 4 weeks following last dose of APX005M	Assess incidence of anti-drug antibodies (ADA)

Trial Locations

Locations (3)

City of Hope; 🇺🇸 Duarte, California, United States

Case Western Reserve University; 🇺🇸 Cleveland, Ohio, United States

Abramson Cancer Center of The University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States