CD40 Agonistic Antibody APX005M in Combination With Nivolumab

Sponsor

Apexigen, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03123783

Collaborator

Bristol-Myers Squibb (Industry)

140

Enrollment

Locations

Arms

40.2

Actual Duration (Months)

6.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer Non Small Cell Lung Cancer Metastatic Metastatic Melanoma Neoplasm of Lung Melanoma	Drug: APX005M Drug: Nivolumab	Phase 1/Phase 2

Detailed Description

APX005M-002 is an open-label Phase 1-2 study and comprises a dose-escalation portion (Phase

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

Study Design

Study Type:

Interventional

Actual Enrollment :

140 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

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.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)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 10, 2017

Actual Primary Completion Date :

Nov 16, 2020

Actual Study Completion Date :

Nov 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1b escalation 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	Drug: APX005M APX005M is a CD40 agonistic monoclonal antibody Drug: Nivolumab Nivolumab is an immune checkpoint (PD-1) blocking antibody Other Names: Opdivo
Experimental: Phase 2 expansion Cohort 1 Immunotherapy naïve, metastatic or locally advanced NSCLC APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks	Drug: APX005M APX005M is a CD40 agonistic monoclonal antibody Drug: Nivolumab Nivolumab is an immune checkpoint (PD-1) blocking antibody Other Names: Opdivo
Experimental: Phase 2 expansion Cohort 2 Metastatic melanoma progressing during treatment with anti-PD-1/PD-L1 therapy APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks	Drug: APX005M APX005M is a CD40 agonistic monoclonal antibody Drug: Nivolumab Nivolumab is an immune checkpoint (PD-1) blocking antibody Other Names: Opdivo
Experimental: Phase 2 expansion Cohort 3 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	Drug: APX005M APX005M is a CD40 agonistic monoclonal antibody Drug: Nivolumab Nivolumab is an immune checkpoint (PD-1) blocking antibody Other Names: Opdivo

Outcome Measures

Primary Outcome Measures

Incidence of dose limiting toxicities [Up to 21 days following first dose of APX005M and nivolumab]
Incidence of dose limiting toxicities in Phase 1
Incidence of adverse events [Through up to approximately 4 weeks following last dose of APX005M and/or nivolumab]
Incidence of adverse events throughout the study
Objective response rate [Every 8 weeks up to approximately 1 year following first dose of APX005M and nivolumab]
Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Secondary Outcome Measures

Blood concentrations of APX005M [Predose, end of infusion, 4, 24, 48 and 168 hours following first and third dose of APX005M]
Blood concentrations of APX005M

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center	Tucson	Arizona	United States	85724
2	City of Hope	Duarte	California	United States	91010
3	Yale University	New Haven	Connecticut	United States	06520
4	Hem-Onc Associates of the Treasure Coast	Port Saint Lucie	Florida	United States	32952
5	University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC)	Baltimore	Maryland	United States	21201
6	Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
7	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
8	SUNY Upstate Medical Hospital	Syracuse	New York	United States	13210
9	University Hospitals Seidman Cancer Center	Cleveland	Ohio	United States	44106
10	Abramson Cancer Center of The University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
11	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
12	Fox Chase Center	Rockledge	Pennsylvania	United States	19046
13	Tennessee Oncology	Nashville	Tennessee	United States	37203
14	Hospital Quirón Dexeus	Barcelona		Spain	08028
15	H. Vall d'Hebron	Barcelona		Spain	08035
16	H. Clinic i Provincial	Barcelona		Spain	08036
17	H. Insular de Gran Canaria	Las Palmas De Gran Canaria		Spain
18	H. Lucus Augusti	Lugo		Spain	27003
19	H. Doce de Octubre	Madrid		Spain	28041
20	H. HM Sanchinnarro	Madrid		Spain	28050
21	H. de Málaga	Málaga		Spain	29010
22	H. General de Valencia	Valencia De Alcántara		Spain	46014
23	H. La Fe	Valencia		Spain	46014