Study of the CD40 Agonistic Monoclonal Antibody APX005M

Cancer Clinical Trial

Official title:

Phase 1 Study to Evaluate the Safety and Tolerability of the CD40 Agonistic Monoclonal Antibody APX005M in Subjects With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02482168
• Other study ID #: APX005M-001
• Status: Completed
• Phase: Phase 1
• Start date: May 2015
• Est. completion date: June 19, 2018

Study information

• Verified date: December 2023
• Source: Apexigen America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: June 19, 2018
• Est. primary completion date: June 13, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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

Related Conditions & MeSH terms

• Cancer
• Carcinoma, Transitional Cell
• Head and Neck Cancer
• Head and Neck Neoplasms
• Melanoma
• MSI-H
• NSCLC
• Urothelial Carcinoma

Intervention

Drug:
• APX005M
APX005M is a CD40 agonistic monoclonal antibody

Locations

Country	Name	City	State
United States	Case Western Reserve University	Cleveland	Ohio
United States	City of Hope	Duarte	California
United States	Abramson Cancer Center of The University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Apexigen America, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities	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	Up to 28 days following first dose of APX005M
Primary	Incidence of adverse events	Incidence and severity of AEs and specific laboratory abnormalities graded according to NCI-CTCAE, v4.03	Through up to approximately 4 weeks following last dose of APX005M
Secondary	Blood concentrations of APX005M	PK parameters of APX005M	Predose, 0.5, 1, 2, 4, 24, 48 and 168 hours following first and third dose of APX005M
Secondary	Presence and titer of anti-APX005M antibodies	Assess incidence of anti-drug antibodies (ADA)	Prior to first dose, approximately 3, 6 and 9 weeks following first dose and approximately 4 weeks following last dose of APX005M
Secondary	Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST)	Efficacy assessments will follow RECIST 1.1.	Every 8 weeks up to approximately 1 year following first dose of APX005M