Cancer, NSCLC, Melanoma, Urothelial Carcinoma, MSI-H, Head and Neck Cancer
Conditions
Keywords
immunotherapy, CD40
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
Interventions
DRUGAPX005M
APX005M is a CD40 agonistic monoclonal antibody
Sponsors
Apexigen America, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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. |
Countries
United States
Outcome results
None listed