Study of the CD40 Agonistic Monoclonal Antibody APX005M

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma; Cancer; Head and Neck Cancer; NSCLC; Urothelial Carcinoma; MSI-H
• Intervention / Treatment: Drug: APX005M

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 Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APX005M every 3 week; Subjects receive APX005M intravenously every 3 week until disease progression, unacceptable toxicity or death.	Drug: APX005M; APX005M is a CD40 agonistic monoclonal antibody
Experimental: APX005M every 2 week; Subjects receive APX005M intravenously every 2 week until disease progression, unacceptable toxicity or death.	Drug: APX005M; APX005M is a CD40 agonistic monoclonal antibody
Experimental: APX005M every 1 week; Subjects receive APX005M intravenously every 1 week until disease progression, unacceptable toxicity or death.	Drug: APX005M; APX005M is a CD40 agonistic monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Apexigen America, Inc.
• Investigators: Study Director: Medical Director, Apexigen America, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): June 13, 2018
• Study Completion (Actual): June 19, 2018

Study Registration Dates

• First Submitted: June 11, 2015
• First Submitted That Met QC Criteria: June 23, 2015
• First Posted (Estimated): June 26, 2015

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: immunotherapy; CD40
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Transitional Cell
• Other Study ID Numbers: APX005M-001