Back to resultsCD40 Agonistic Antibody APX005M in Combination With Nivolumab
Primary Purpose
Cancer, Non Small Cell Lung Cancer Metastatic, Metastatic Melanoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
APX005M
Nivolumab
Sponsored by
About this trial
This is an interventional treatment trial for Cancer focused on measuring CD40, Immunotherapy, Nivolumab, APX005M, PD-1
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed, immunotherapy naïve or PD-1/PD-L1 pre-treated, metastatic or locally advanced non-small cell lung cancer not amenable to curative treatment. Subjects may be treatment naive or could have received one prior platinum based chemotherapy for non-small cell lung cancer and subjects with a documented activating mutation (e.g., EGFR, ALK, ROS) must also have received the appropriate therapy and progressed
- Histologically or cytologically confirmed unresectable or metastatic melanoma that had confirmed progressive disease during treatment with anti-PD-1/PD-L1 therapy. Subjects with BRAF activating mutation could have also received a BRAF inhibitor and/or MEK inhibitor regimen prior to anti-PD-1/PD-L1 therapy.
- Measurable disease by RECIST 1.1
- ECOG performance status of 0 or 1
- Adequate bone marrow, liver and kidney function
- Negative pregnancy test for women of child bearing potential
- Agreement to use effective methods of contraception per the protocol requirements
Exclusion Criteria:
- Previous exposure to any immunomodulatory agents (e.g., anti- CD40, anti-PD-1/PD-L1, anti-CTLA-4, IDO inhibitors) except PD-1/PD-L1 targeting agents in the subsets of patients that must have previous treatment with anti-PD-1/PD-L1 therapy
- Second malignancy (solid or hematologic) within the past 3 years except locally curable cancers that have been apparently cured
- Active, known, clinically serious infections within the 14 days prior to first dose of investigational product
- Use of systemic corticosteroids or other systemic immunosuppressive drugs
- Active, known or suspected autoimmune disease
- History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis
- History of interstitial lung disease
- History of life-threatening toxicity related to prior anti-PD-1/PD-L1 treatment for subjects with metastatic melanoma or NSCLC.
Sites / Locations
- University of Arizona Cancer Center
- City of Hope
- Yale University
- Hem-Onc Associates of the Treasure Coast
- University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC)
- Nebraska Cancer Specialists
- University of Nebraska Medical Center
- SUNY Upstate Medical Hospital
- University Hospitals Seidman Cancer Center
- Abramson Cancer Center of The University of Pennsylvania
- Fox Chase Cancer Center
- Fox Chase Center
- Tennessee Oncology
- Hospital Quirón Dexeus
- H. Vall d'Hebron
- H. Clinic i Provincial
- H. Insular de Gran Canaria
- H. Lucus Augusti
- H. Doce de Octubre
- H. HM Sanchinnarro
- H. de Málaga
- H. General de Valencia
- H. La Fe
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Phase 1b escalation
Phase 2 expansion Cohort 1
Phase 2 expansion Cohort 2
Phase 2 expansion Cohort 3
Arm Description
Non-small cell lung cancer (NSCLC) or metastatic melanoma APX005M escalated from 0.03 to 0.1 to 0.3 mg/kg and nivolumab 360 mg every 3 weeks
Immunotherapy naïve, metastatic or locally advanced NSCLC APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks
Metastatic melanoma progressing during treatment with anti-PD-1/PD-L1 therapy APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks
Metastatic or locally advanced NSCLC progressing during treatment with anti-PD-1/PD-L1: Group A: best response of progressive disease or with stable disease < 16 weeks Group B: tumor response or with stable disease ≥ 16 weeks APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks
Outcomes
Primary Outcome Measures
Incidence of dose limiting toxicities
Incidence of dose limiting toxicities in Phase 1
Incidence of adverse events
Incidence of adverse events throughout the study
Objective response rate
Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Secondary Outcome Measures
Blood concentrations of APX005M
Blood concentrations of APX005M
Full Information
NCT ID
NCT03123783
First Posted
April 17, 2017
Last Updated
December 3, 2021
Sponsor
Apexigen America, Inc.
Collaborators
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT03123783
Brief Title
CD40 Agonistic Antibody APX005M in Combination With Nivolumab
Official Title
A Study to Evaluate the Safety and Efficacy of the CD40 Agonistic Antibody APX005M Administered in Combination With Nivolumab in Subjects With Non-small Cell Lung Cancer and Subjects With Metastatic Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
July 10, 2017 (Actual)
Primary Completion Date
November 16, 2020 (Actual)
Study Completion Date
November 16, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Apexigen America, Inc.
Collaborators
Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is a Phase 1-2 open-label dose escalation study of the immuno-activating monoclonal antibody APX005M administered in combination with nivolumab to adult subjects with non-small cell lung cancer or metastatic melanoma. The Phase 1 portion is intended to establish the maximum tolerated dose and the recommended phase 2 dose of APX005M when administered in combination with nivolumab. The Phase 2 portion of the study will evaluate safety and efficacy of the combination.
Detailed Description
APX005M-002 is an open-label Phase 1-2 study and comprises a dose-escalation portion (Phase 1) followed by a Phase 2 tumor specific portion.
Eligible subjects with non-small cell lung cancer or metastatic melanoma will receive intravenous APX005M in combination with nivolumab until disease progression, unacceptable toxicity or death, whichever occurs first.
Study objectives include:
Determine the maximum tolerated dose and the recommended phase 2 dose of APX005M when given in combination with nivolumab
Evaluate safety of the APX005M and nivolumab combination
Evaluate the objective response rate, duration of response and median PFS by RECIST 1.1 in subjects with non-small cell lung cancer or metastatic melanoma receiving APX005M in combination with nivolumab
Determine the PK of APX005M
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Non Small Cell Lung Cancer Metastatic, Metastatic Melanoma, Neoplasm of Lung, Melanoma
Keywords
CD40, Immunotherapy, Nivolumab, APX005M, PD-1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Phase 1b dose escalation with up to 4 sequential dose levels. Followed by Phase 2 dose expansion at Recommended Phase 2 Dose in 3 parallel disease cohorts.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
140 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1b escalation
Arm Type
Experimental
Arm Description
Non-small cell lung cancer (NSCLC) or metastatic melanoma
APX005M escalated from 0.03 to 0.1 to 0.3 mg/kg and nivolumab 360 mg every 3 weeks
Arm Title
Phase 2 expansion Cohort 1
Arm Type
Experimental
Arm Description
Immunotherapy naïve, metastatic or locally advanced NSCLC
APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks
Arm Title
Phase 2 expansion Cohort 2
Arm Type
Experimental
Arm Description
Metastatic melanoma progressing during treatment with anti-PD-1/PD-L1 therapy
APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks
Arm Title
Phase 2 expansion Cohort 3
Arm Type
Experimental
Arm Description
Metastatic or locally advanced NSCLC progressing during treatment with anti-PD-1/PD-L1:
Group A: best response of progressive disease or with stable disease < 16 weeks
Group B: tumor response or with stable disease ≥ 16 weeks
APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks
Intervention Type
Drug
Intervention Name(s)
APX005M
Intervention Description
APX005M is a CD40 agonistic monoclonal antibody
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo
Intervention Description
Nivolumab is an immune checkpoint (PD-1) blocking antibody
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities
Description
Incidence of dose limiting toxicities in Phase 1
Time Frame
Up to 21 days following first dose of APX005M and nivolumab
Title
Incidence of adverse events
Description
Incidence of adverse events throughout the study
Time Frame
Through up to approximately 4 weeks following last dose of APX005M and/or nivolumab
Title
Objective response rate
Description
Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time Frame
Every 8 weeks up to approximately 1 year following first dose of APX005M and nivolumab
Secondary Outcome Measure Information:
Title
Blood concentrations of APX005M
Description
Blood concentrations of APX005M
Time Frame
Predose, end of infusion, 4, 24, 48 and 168 hours following first and third dose of APX005M
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed, immunotherapy naïve or PD-1/PD-L1 pre-treated, metastatic or locally advanced non-small cell lung cancer not amenable to curative treatment. Subjects may be treatment naive or could have received one prior platinum based chemotherapy for non-small cell lung cancer and subjects with a documented activating mutation (e.g., EGFR, ALK, ROS) must also have received the appropriate therapy and progressed
Histologically or cytologically confirmed unresectable or metastatic melanoma that had confirmed progressive disease during treatment with anti-PD-1/PD-L1 therapy. Subjects with BRAF activating mutation could have also received a BRAF inhibitor and/or MEK inhibitor regimen prior to anti-PD-1/PD-L1 therapy.
Measurable disease by RECIST 1.1
ECOG performance status of 0 or 1
Adequate bone marrow, liver and kidney function
Negative pregnancy test for women of child bearing potential
Agreement to use effective methods of contraception per the protocol requirements
Exclusion Criteria:
Previous exposure to any immunomodulatory agents (e.g., anti- CD40, anti-PD-1/PD-L1, anti-CTLA-4, IDO inhibitors) except PD-1/PD-L1 targeting agents in the subsets of patients that must have previous treatment with anti-PD-1/PD-L1 therapy
Second malignancy (solid or hematologic) within the past 3 years except locally curable cancers that have been apparently cured
Active, known, clinically serious infections within the 14 days prior to first dose of investigational product
Use of systemic corticosteroids or other systemic immunosuppressive drugs
Active, known or suspected autoimmune disease
History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis
History of interstitial lung disease
History of life-threatening toxicity related to prior anti-PD-1/PD-L1 treatment for subjects with metastatic melanoma or NSCLC.
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
University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Hem-Onc Associates of the Treasure Coast
City
Port Saint Lucie
State/Province
Florida
ZIP/Postal Code
32952
Country
United States
Facility Name
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Nebraska Cancer Specialists
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68130
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
SUNY Upstate Medical Hospital
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
University Hospitals Seidman Cancer Center
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
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Fox Chase Center
City
Rockledge
State/Province
Pennsylvania
ZIP/Postal Code
19046
Country
United States
Facility Name
Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Hospital Quirón Dexeus
City
Barcelona
ZIP/Postal Code
08028
Country
Spain
Facility Name
H. Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
H. Clinic i Provincial
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
H. Insular de Gran Canaria
City
Las Palmas De Gran Canaria
Country
Spain
Facility Name
H. Lucus Augusti
City
Lugo
ZIP/Postal Code
27003
Country
Spain
Facility Name
H. Doce de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
H. HM Sanchinnarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
H. de Málaga
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
H. General de Valencia
City
Valencia De Alcántara
ZIP/Postal Code
46014
Country
Spain
Facility Name
H. La Fe
City
Valencia
ZIP/Postal Code
46014
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
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CD40 Agonistic Antibody APX005M in Combination With Nivolumab
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