Study of the CD40 Agonistic Monoclonal Antibody APX005M

Study Overview
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Brief Summary
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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
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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

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

Conditions
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MSI-H, Cancer, NSCLC, Melanoma, Urothelial Carcinoma, Head and Neck Cancer

Intervention / Treatment
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* Drug: APX005M


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, CD40