Clinical trial NCT03123783: CD40 Agonistic Antibody APX005M (Sotigalimab) 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cancer
Non Small Cell Lung Cancer Metastatic
Metastatic Melanoma
Neoplasm of Lung
Melanoma
Keywords: CD40
Immunotherapy
Nivolumab
APX005M
PD-1
Lead sponsor: Apexigen America, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2017-04-21
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

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

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 progressed during treatment with an anti-PD-1/PD-L1 therapy and had confirmation of PD\>=4 weeks later. 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.

Primary outcomes:
measure: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
timeFrame: Up to 21 days following first dose of APX005M and nivolumab
measure: Maximum Tolerated Dose (MTD) of APX005M + Nivolumab (Phase 1b)
timeFrame: Up to 21 days following first dose of APX005M and nivolumab
measure: Phase 2 Evaluate the Objective Response Rate (ORR) by RECIST 1.1 and iRECIST in Each Cohort / Group
timeFrame: From start of the treatment (Day 1) until disease progression, withdrawal of consent, death, initiation of any anticancer therapy, lost to follow-up, or termination by the Sponsor, whichever comes first (for Phase 2: maximum up to 27 months)
Secondary outcomes:
measure: Safety of the APX005M and Nivolumab Combination (Phase 2)
timeFrame: Day 1 up to 30 days (or 100 days for SAEs and AEs with potential immunologic etiology) following the after the last dose of APX005M and/or nivolumab (from start of treatment up to 27 months)
measure: Duration of Response (DOR) as Per RECIST 1.1(Phase 2)
timeFrame: Maximum up to 25 months
measure: Median Progression-free Survival (PFS) (Phase 2)
timeFrame: From start of treatment (Day 1) up to 27 months
measure: 6-month PFS Rate (Phase 2)
timeFrame: * Outcome Measure Time Frame From start of treatment (Day 1) to 6 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Port Saint Lucie
country: United States
facility: Hem-Onc Associates of the Treasure Coast
state: Florida
city: Baltimore
country: United States
facility: University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC)
state: Maryland
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Syracuse
country: United States
facility: SUNY Upstate Medical Hospital
state: New York
city: Cleveland
country: United States
facility: University Hospitals Seidman Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center of The University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Rockledge
country: United States
facility: Fox Chase Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Barcelona
country: Spain
facility: Hospital Quirón Dexeus
city: Barcelona
country: Spain
facility: H. Vall d'Hebron
city: Barcelona
country: Spain
facility: H. Clinic i Provincial
city: Las Palmas De Gran Canaria
country: Spain
facility: H. Insular de Gran Canaria
city: Lugo
country: Spain
facility: H. Lucus Augusti
city: Madrid
country: Spain
facility: H. Doce de Octubre
city: Madrid
country: Spain
facility: H. HM Sanchinnarro
city: Málaga
country: Spain
facility: H. de Málaga
city: Valencia De Alcántara
country: Spain
facility: H. General de Valencia
city: Valencia
country: Spain
facility: H. La Fe
Study officials:
affiliation: Pyxis Oncology, Inc
name: Medical Director
role: STUDY_DIRECTOR
References: