CD40 Agonistic Antibody APX005M (Sotigalimab) in Combination With Nivolumab

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.

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

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.