Clinical trial NCT02482168: Study of the CD40 Agonistic Monoclonal Antibody APX005M
Official title: Phase 1 Study to Evaluate the Safety and Tolerability of the CD40 Agonistic Monoclonal Antibody APX005M in Subjects With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
NSCLC
Melanoma
Urothelial Carcinoma
MSI-H
Head and Neck Cancer
Keywords: immunotherapy
CD40
Lead sponsor: Apexigen America, Inc.
Sponsor class: INDUSTRY
First posted: 2015-06-26
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of dose limiting toxicities
timeFrame: Up to 28 days following first dose of APX005M
measure: Incidence of adverse events
timeFrame: Through up to approximately 4 weeks following last dose of APX005M
Secondary outcomes:
measure: Blood concentrations of APX005M
timeFrame: Predose, 0.5, 1, 2, 4, 24, 48 and 168 hours following first and third dose of APX005M
measure: Presence and titer of anti-APX005M antibodies
timeFrame: Prior to first dose, approximately 3, 6 and 9 weeks following first dose and approximately 4 weeks following last dose of APX005M
measure: Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Every 8 weeks up to approximately 1 year following first dose of APX005M
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center of The University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Apexigen America, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: