CD40 Agonistic Antibody APX005M (Sotigalimab) in Combination With Nivolumab

Apexigen

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Drug: APX005M; Drug: Nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03123783

APX005M-002

Details and patient eligibility

About

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.

Full 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

Enrollment: 140 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

140 participants in 6 patient groups

Phase 1b escalation 0.03 mg/kg

Experimental group

Description:

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

Treatment:

Drug: APX005M

Drug: Nivolumab

Phase 1b escalation 0.1 mg/kg

Experimental group

Description:

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

Treatment:

Drug: APX005M

Drug: Nivolumab

Phase 1b escalation 0.3 mg/kg

Experimental group

Description:

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

Treatment:

Drug: APX005M

Drug: Nivolumab

Phase 2 expansion Cohort 1

Experimental group

Description:

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

Treatment:

Drug: APX005M

Drug: Nivolumab

Phase 2 expansion Cohort 2

Experimental group

Description:

Metastatic melanoma progressing during treatment with anti-PD-1/PD-L1 therapy APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks

Treatment:

Drug: APX005M

Drug: Nivolumab

Phase 2 expansion Cohort 3

Experimental group

Description:

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

Treatment:

Drug: APX005M

Drug: Nivolumab