Study of the CD40 Agonistic Monoclonal Antibody APX005M

• ClinicalTrials.gov Identifier: NCT02482168
• Recruitment Status: Completed
• First Posted: June 26, 2015
• Last Update Posted: April 28, 2020
• Sponsor: Apexigen, Inc.
• Information provided by (Responsible Party): Apexigen, Inc.

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.

Condition or disease	Intervention/treatment	Phase
Cancer; NSCLC; Melanoma; Urothelial Carcinoma; MSI-H; Head and Neck Cancer	Drug: APX005M	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1 Study to Evaluate the Safety and Tolerability of the CD40 Agonistic Monoclonal Antibody APX005M in Subjects With Solid Tumors
• Study Start Date: May 2015
• Actual Primary Completion Date: June 13, 2018
• Actual Study Completion Date: June 19, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose limiting toxicities [ Time Frame: 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
2. Incidence of adverse events [ Time Frame: 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 Outcome Measures :

1. Blood concentrations of APX005M [ Time Frame: Predose, 0.5, 1, 2, 4, 24, 48 and 168 hours following first and third dose of APX005M ]
   PK parameters of APX005M
2. Presence and titer of anti-APX005M antibodies [ Time Frame: 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)
3. Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Every 8 weeks up to approximately 1 year following first dose of APX005M ]
   Efficacy assessments will follow RECIST 1.1.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, California

City of Hope

Duarte, California, United States, 91010

United States, Ohio

Case Western Reserve University

Cleveland, Ohio, United States, 44106

United States, Pennsylvania

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Apexigen, Inc.

Investigators

• Study Director: Medical Director; Apexigen, Inc.

More Information

• Responsible Party: Apexigen, Inc.
• ClinicalTrials.gov Identifier: NCT02482168
• Other Study ID Numbers: APX005M-001
• First Posted: June 26, 2015
• Last Update Posted: April 28, 2020
• Last Verified: April 2018

Keywords provided by Apexigen, Inc.:

immunotherapy; CD40

Additional relevant MeSH terms:

Head and Neck Neoplasms; Carcinoma, Transitional Cell; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial