CD40 Agonistic Antibody APX005M (Sotigalimab) in Combination With Nivolumab

Browse trials for

• Neoplasms 9,610
• Melanoma 3,073
• Lung Neoplasms 7,333

Keywords

• CD40
• Immunotherapy
• Nivolumab
• APX005M
• PD-1

Neoplasms

9,610 studies on the registry are indexed under Neoplasms; 2,508 are open to participants now.

This study's enrollment of 140 is above the median of 50 across 7,429 interventional studies indexed under Neoplasms.

Lead sponsor

Apexigen America, Inc. is the lead sponsor of 4 studies on the registry; none are open to participants now.

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

  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

  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

  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

  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

  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

  Drug: APX005M · Drug: Nivolumab

Interventions

• DrugAPX005M

  APX005M is a CD40 agonistic monoclonal antibody

• DrugNivolumab

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

  Also known as: Opdivo

Primary outcomes

1. 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.

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

2. 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.

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

3. 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.

   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)

Secondary outcomes

1. Safety of the APX005M and Nivolumab Combination (Phase 2)

   Number of participants with TEAEs are reported.

   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)

2. 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.

   Time frame: Maximum up to 25 months

3. 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.

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

4. 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.

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

Baseline characteristics

Study documents

• Study protocol · Oct 10, 2019
• Statistical analysis plan · Feb 4, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No