CD40 Agonistic Antibody APX005M (Sotigalimab) in Combination With Nivolumab

• ClinicalTrials.gov Identifier: NCT03123783
• Recruitment Status: Completed
• First Posted: April 21, 2017
• Results First Posted: December 5, 2023
• Last Update Posted: December 26, 2023
• Sponsor: Apexigen America, Inc.
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Apexigen America, Inc.

Tracking Information

• First Submitted Date: April 17, 2017
• First Posted Date: April 21, 2017
• Results First Submitted Date: November 15, 2022
• Results First Posted Date: December 5, 2023
• Last Update Posted Date: December 26, 2023
• Actual Study Start Date: July 10, 2017
• Actual Primary Completion Date: November 16, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 13, 2023)

• 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.
• 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.
• 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.

Original Primary Outcome Measures (submitted: April 18, 2017)

• Incidence of dose limiting toxicities [ Time Frame: Up to 21 days following first dose of APX005M and nivolumab ]
  Incidence of dose limiting toxicities in Phase 1
• Incidence of adverse events [ Time Frame: Through up to approximately 4 weeks following last dose of APX005M and/or nivolumab ]
  Incidence of adverse events throughout the study
• Objective response rate [ Time Frame: 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)

Current Secondary Outcome Measures (submitted: November 13, 2023)

• 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.
• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: April 18, 2017)

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

Blood concentrations of APX005M

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

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.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

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

Intervention

• Drug: APX005M
  APX005M is a CD40 agonistic monoclonal antibody
• Drug: Nivolumab
  Nivolumab is an immune checkpoint (PD-1) blocking antibody
  Other Name: Opdivo

Study Arms

• 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

  Interventions:

  • Drug: APX005M
  • Drug: Nivolumab
• 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

  Interventions:

  • Drug: APX005M
  • Drug: Nivolumab
• 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

  Interventions:

  • Drug: APX005M
  • Drug: Nivolumab
• 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

  Interventions:

  • Drug: APX005M
  • Drug: Nivolumab
• 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

  Interventions:

  • Drug: APX005M
  • Drug: Nivolumab
• 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
  Interventions:

  • Drug: APX005M
  • Drug: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 29, 2021): 140
• Original Estimated Enrollment (submitted: April 18, 2017): 99
• Actual Study Completion Date: November 16, 2020
• Actual Primary Completion Date: November 16, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain, United States

Administrative Information

• NCT Number: NCT03123783
• Other Study ID Numbers: APX005M-002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Apexigen America, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Apexigen America, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Bristol-Myers Squibb

Investigators

• Study Director: Medical Director; Pyxis Oncology, Inc

• PRS Account: Apexigen America, Inc.
• Verification Date: December 2023