Study of the CD40 Agonistic Monoclonal Antibody APX005M
Primary Purpose
Cancer, NSCLC, Melanoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
APX005M
Sponsored by
About this trial
This is an interventional treatment trial for Cancer focused on measuring immunotherapy, CD40
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
Sites / Locations
- City of Hope
- Case Western Reserve University
- Abramson Cancer Center of The University of Pennsylvania
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
APX005M every 3 week
APX005M every 2 week
APX005M every 1 week
Arm Description
Subjects receive APX005M intravenously every 3 week until disease progression, unacceptable toxicity or death.
Subjects receive APX005M intravenously every 2 week until disease progression, unacceptable toxicity or death.
Subjects receive APX005M intravenously every 1 week until disease progression, unacceptable toxicity or death.
Outcomes
Primary Outcome Measures
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
Incidence of adverse events
Incidence and severity of AEs and specific laboratory abnormalities graded according to NCI-CTCAE, v4.03
Secondary Outcome Measures
Blood concentrations of APX005M
PK parameters of APX005M
Presence and titer of anti-APX005M antibodies
Assess incidence of anti-drug antibodies (ADA)
Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST)
Efficacy assessments will follow RECIST 1.1.
Full Information
NCT ID
NCT02482168
First Posted
June 11, 2015
Last Updated
September 18, 2023
Sponsor
Apexigen America, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02482168
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
June 13, 2018 (Actual)
Study Completion Date
June 19, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Apexigen America, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, NSCLC, Melanoma, Urothelial Carcinoma, MSI-H, Head and Neck Cancer
Keywords
immunotherapy, CD40
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
APX005M every 3 week
Arm Type
Experimental
Arm Description
Subjects receive APX005M intravenously every 3 week until disease progression, unacceptable toxicity or death.
Arm Title
APX005M every 2 week
Arm Type
Experimental
Arm Description
Subjects receive APX005M intravenously every 2 week until disease progression, unacceptable toxicity or death.
Arm Title
APX005M every 1 week
Arm Type
Experimental
Arm Description
Subjects receive APX005M intravenously every 1 week until disease progression, unacceptable toxicity or death.
Intervention Type
Drug
Intervention Name(s)
APX005M
Intervention Description
APX005M is a CD40 agonistic monoclonal antibody
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities
Description
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
Time Frame
Up to 28 days following first dose of APX005M
Title
Incidence of adverse events
Description
Incidence and severity of AEs and specific laboratory abnormalities graded according to NCI-CTCAE, v4.03
Time Frame
Through up to approximately 4 weeks following last dose of APX005M
Secondary Outcome Measure Information:
Title
Blood concentrations of APX005M
Description
PK parameters of APX005M
Time Frame
Predose, 0.5, 1, 2, 4, 24, 48 and 168 hours following first and third dose of APX005M
Title
Presence and titer of anti-APX005M antibodies
Description
Assess incidence of anti-drug antibodies (ADA)
Time Frame
Prior to first dose, approximately 3, 6 and 9 weeks following first dose and approximately 4 weeks following last dose of APX005M
Title
Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST)
Description
Efficacy assessments will follow RECIST 1.1.
Time Frame
Every 8 weeks up to approximately 1 year following first dose of APX005M
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Apexigen America, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Abramson Cancer Center of The University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of the CD40 Agonistic Monoclonal Antibody APX005M
We'll reach out to this number within 24 hrs