CD40 Agonistic Antibody APX005M (Sotigalimab) in Combination With Nivolumab

NCT03123783 | Completed Phase 1 Results FDA Drug

• 1 other identifier: APX005M-002
• Study Type: interventional
• Target: 140
• Locations: 2 countries
• Sites: 23

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.

Conditions

Cancer; Non Small Cell Lung Cancer Metastatic; Metastatic Melanoma; Neoplasm of Lung; Melanoma

Keywords

CD40; Immunotherapy; Nivolumab; APX005M; PD-1

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Safety of the APX005M and Nivolumab Combination (Phase 2)

  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)

  Maximum up to 25 months

• Median Progression-free Survival (PFS) (Phase 2)

  From start of treatment (Day 1) up to 27 months

• 6-month PFS Rate (Phase 2)

  * Outcome Measure Time Frame From start of treatment (Day 1) to 6 months

Study Arms (6)

Phase 1b escalation 0.03 mg/kg

EXPERIMENTAL

Non-small cell lung cancer (NSCLC) or metastatic melanoma APX005M 0.03 mg/kg and nivolumab 360 mg every 3 weeks

Drug: APX005M; Drug: Nivolumab

Phase 1b escalation 0.1 mg/kg

EXPERIMENTAL

Non-small cell lung cancer (NSCLC) or metastatic melanoma APX005M 0.1 mg/kg and nivolumab 360 mg every 3 weeks

Drug: APX005M; Drug: Nivolumab

Phase 1b escalation 0.3 mg/kg

EXPERIMENTAL

Non-small cell lung cancer (NSCLC) or metastatic melanoma APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks

Drug: APX005M; Drug: Nivolumab

Phase 2 expansion Cohort 1

EXPERIMENTAL

Immunotherapy naïve, metastatic or locally advanced NSCLC APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks

Drug: APX005M; Drug: Nivolumab

Phase 2 expansion Cohort 2

EXPERIMENTAL

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; Drug: Nivolumab

Phase 2 expansion Cohort 3

EXPERIMENTAL

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; Drug: Nivolumab

Interventions

APX005M DRUG

APX005M is a CD40 agonistic monoclonal antibody

Phase 1b escalation 0.03 mg/kg; Phase 1b escalation 0.1 mg/kg; Phase 1b escalation 0.3 mg/kg; Phase 2 expansion Cohort 1; Phase 2 expansion Cohort 2; Phase 2 expansion Cohort 3

Nivolumab DRUG

Nivolumab is an immune checkpoint (PD-1) blocking antibody

Also known as: Opdivo

Phase 1b escalation 0.03 mg/kg; Phase 1b escalation 0.1 mg/kg; Phase 1b escalation 0.3 mg/kg; Phase 2 expansion Cohort 1; Phase 2 expansion Cohort 2; Phase 2 expansion Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Apexigen America, Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (23)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Hem-Onc Associates of the Treasure Coast

Port Saint Lucie, Florida, 32952, United States

Location

University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC)

Baltimore, Maryland, 21201, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

SUNY Upstate Medical Hospital

Syracuse, New York, 13210, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Fox Chase Center

Rockledge, Pennsylvania, 19046, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Hospital Quirón Dexeus

Barcelona, 08028, Spain

Location

H. Vall d'Hebron

Barcelona, 08035, Spain

Location

H. Clinic i Provincial

Barcelona, 08036, Spain

Location

H. Insular de Gran Canaria

Las Palmas de Gran Canaria, Spain

Location

H. Lucus Augusti

Lugo, 27003, Spain

Location

H. Doce de Octubre

Madrid, 28041, Spain

Location

H. HM Sanchinnarro

Madrid, 28050, Spain

Location

H. de Málaga

Málaga, 29010, Spain

Location

H. La Fe

Valencia, 46014, Spain

Location

H. General de Valencia

Valencia de Alcántara, 46014, Spain

Location

MeSH Terms

Conditions

Neoplasms; Melanoma; Lung Neoplasms

Interventions

sotigalimab; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

In the AE section, DL3 participant data had no DLTs; AE data collected from DL3 was also added to Phase 2.

Results Point of Contact

• Title: Pyxis Oncology Clinical Operations
• Organization: Pyxis Oncology, Inc.

clinicaltrials@pyxisoncology.com

(339) 545 8252

Study Officials

• Medical Director

  Pyxis Oncology, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 17, 2017
• First Posted: April 21, 2017
• Study Start: July 10, 2017
• Primary Completion: November 16, 2020
• Study Completion: November 16, 2020
• Last Updated: December 26, 2023
• Results First Posted: December 5, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (10); US (13)