CD40 Agonistic Antibody APX005M (Sotigalimab) in Combination With Nivolumab

December 21, 2023 updated by: Apexigen America, Inc.

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
140

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
Time Frame: Up to 21 days following first dose of APX005M and nivolumab

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)
Time Frame: Up to 21 days following first dose of APX005M and nivolumab
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
Time Frame: 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)
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety of the APX005M and Nivolumab Combination (Phase 2)
Time Frame: 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)
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)
Time Frame: Maximum up to 25 months
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)
Time Frame: From start of treatment (Day 1) up to 27 months
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)
Time Frame: * Outcome Measure Time Frame From start of treatment (Day 1) to 6 months
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Apexigen America, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bristol-Myers Squibb

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Director, Pyxis Oncology, Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 10, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 16, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 16, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 17, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 21, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 26, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 21, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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