CD40 Agonistic Antibody APX005M (Sotigalimab) in Combination With Nivolumab

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma; Cancer; Metastatic Melanoma; Non Small Cell Lung Cancer Metastatic; Neoplasm of Lung
• Intervention / Treatment: Drug: APX005M; Drug: Nivolumab

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

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08028
    • Hospital Quiron Dexeus
  • Barcelona, Spain, 08035
    • H. Vall d'Hebron
  • Barcelona, Spain, 08036
    • H. Clínic i Provincial
  • Las Palmas De Gran Canaria, Spain
    • H. Insular de Gran Canaria
  • Lugo, Spain, 27003
    • H. Lucus Augusti
  • Madrid, Spain, 28041
    • H. Doce de Octubre
  • Madrid, Spain, 28050
    • H. HM Sanchinnarro
  • Málaga, Spain, 29010
    • H. de Málaga
  • Valencia, Spain, 46014
    • H. La Fe
  • Valencia De Alcántara, Spain, 46014
    • H. General de Valencia
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • California
    • Duarte, California, United States, 91010
      • City Of Hope
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Florida
    • Port Saint Lucie, Florida, United States, 32952
      • Hem-Onc Associates of the Treasure Coast
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC)
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Seidman Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of The University of Pennsylvania
    • Rockledge, Pennsylvania, United States, 19046
      • Fox Chase Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 1b escalation 0.03 mg/kg; Non-small cell lung cancer (NSCLC) or metastatic melanoma APX005M 0.03 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 1b escalation 0.1 mg/kg; Non-small cell lung cancer (NSCLC) or metastatic melanoma APX005M 0.1 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 1b escalation 0.3 mg/kg; Non-small cell lung cancer (NSCLC) or metastatic melanoma 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	Drug: APX005M; APX005M is a CD40 agonistic monoclonal antibody; Drug: Nivolumab; Nivolumab is an immune checkpoint (PD-1) blocking antibody; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Dose-limiting Toxicities (DLTs)	All toxicities were graded according to the NCI-CTCAE version 4.03. DLT was defined as any of the following events attributed to APX005M and nivolumab combination: Grade 4 hematologic toxicity lasting ≥ 7 days (except asymptomatic lymphopenia); Grade 3 or 4 neutropenia with a single temperature of >38.3◦ C (101◦ F) or a sustained temperature of ≥38◦ C (100.4◦ F) for more than one hour; Grade 4 thrombocytopenia or Grade ≥3 thrombocytopenia with signs or symptoms of bleeding or requiring platelet transfusion; Grade 4 non-hematologic toxicity; Grade 3 non-hematologic toxicity lasting >3 days despite optimal supportive care; Any Grade ≥ 3 non-hematologic laboratory value if: medical intervention is required to treat the subject, abnormality leads to hospitalization, or abnormality persists for >1 week; Failure to recover from a treatment-related AE to baseline or ≤ Grade 1 within 12 weeks of last dose of investigational product; Grade 5 toxicity.	Up to 21 days following first dose of APX005M and nivolumab
Maximum Tolerated Dose (MTD) of APX005M + Nivolumab (Phase 1b)	Establish the MTD dose of APX005M combined with 360 mg of nivolumab for which for which < 33% of DLT- evaluable participants experience a DLT. In Phase 1b, the RP2D was based on the overall safety and tolerability of the combination of APX005M and nivolumab by testing increasing doses up to 0.3 mg/kg APX005M + nivolumab.	Up to 21 days following first dose of APX005M and nivolumab
Phase 2 Evaluate the Objective Response Rate (ORR) by RECIST 1.1 and iRECIST in Each Cohort / Group	ORR defined as the rate of patients who show as best overall response; either a complete response (CR) or a partial response (PR). The ORR can be evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. using computed tomography (CT) scans/magnetic resonance imaging (MRI). Per RECIST v1.1, for target lesions and assessed by imaging: Complete Response, (CR), Disappearance of all target lesions and nontarget (NT) lesions; Partial Response (PR), >30% decrease in the sum of the longest diameter of target lesions and no PD in NT lesions or new lesions; Objective Response Rate (ORR)=CR + PR.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the APX005M and Nivolumab Combination (Phase 2)	Number of participants with TEAEs are reported.	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)
Duration of Response (DOR) as Per RECIST 1.1(Phase 2)	Duration of Response is defined as the time from the first evidence of confirmed partial response (PR) or better by Per RECIST v1.1 to disease progression or death due to any cause; in subjects alive without progressive disease (PD), DOR was censored on the date of the last tumor assessment. PD is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Maximum up to 25 months
Median Progression-free Survival (PFS) (Phase 2)	Progression-free Survival (PFS) in each cohort, measured from first dose to the earlier of PD (by RECIST 1.1) or death due to any cause, whichever occurs first.	From start of treatment (Day 1) up to 27 months
6-month PFS Rate (Phase 2)	PFS rate in each cohort, measured from first dose to the earlier of PD (by RECIST 1.1) or death due to any cause, whichever occurs first.	* Outcome Measure Time Frame From start of treatment (Day 1) to 6 months

Collaborators and Investigators

• Sponsor: Apexigen America, Inc.
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Medical Director, Pyxis Oncology, Inc

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2017
• Primary Completion (Actual): November 16, 2020
• Study Completion (Actual): November 16, 2020

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: April 18, 2017
• First Posted (Actual): April 21, 2017

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Nivolumab; Immunotherapy; PD-1; CD40; APX005M
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: APX005M-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No