CD40 Agonistic Antibody APX005M (Sotigalimab) in Combination With 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.

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

Population: All participants in the safety population who received at least 1 dose of study drug in the escalation cohorts (APX005M 0.03 mg/kg + nivolumab; APX005M 0.1 mg/kg + nivolumab; APX005M 0.3 mg/kg + 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.

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

Population: All participants in the safety population who received at least 1 dose of study drug in the escalation cohorts (APX005M 0.03 mg/kg + nivolumab; APX005M 0.1 mg/kg + nivolumab; APX005M 0.3 mg/kg + nivolumab)

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)

Population: Cohort 1: immunotherapy naïve metastatic or locally advanced NSCLC, Cohort 2: unresectable or metastatic melanoma that progressed during treatment with anti-PD-1/PD-L1 therapy and had confirmation of PD ≥4 weeks, Cohort 3: PD1-NSCLC metastatic or locally advanced NSCLC not amenable to curative treatment that progressed during prior treatment with anti-PD-1/PD-L1 therapy. Cohort 3A: best response of PD or with SD \<16 weeks, Cohort 3B includes PD1-NSCLC with tumor response or with SD ≥ 16 weeks

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

Population: Cohort 1: immunotherapy naïve metastatic or locally advanced NSCLC, Cohort 2: unresectable or metastatic melanoma that progressed during treatment with anti-PD-1/PD-L1 therapy and had confirmation of PD ≥4 weeks, Cohort 3: PD1-NSCLC metastatic or locally advanced NSCLC not amenable to curative treatment that progressed during prior treatment with anti-PD-1/PD-L1 therapy. Cohort 3A: best response of PD or with SD \<16 weeks, Cohort 3B includes PD1-NSCLC with tumor response or with SD ≥ 16 weeks.

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

Population: Cohort 1: immunotherapy naïve metastatic or locally advanced NSCLC, Cohort 2: unresectable or metastatic melanoma that progressed during treatment with anti-PD-1/PD-L1 therapy and had confirmation of PD ≥4 week. Cohort 3A/PD1-NSCLC and Cohort 3B/PD1 NSCLC had no objective response and therefore DOR could not be assessed.

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

Population: Cohort 1: immunotherapy naïve metastatic or locally advanced NSCLC, Cohort 2: unresectable or metastatic melanoma that progressed during treatment with anti-PD-1/PD-L1 therapy and had confirmation of PD ≥4 weeks, Cohort 3: PD1-NSCLC metastatic or locally advanced NSCLC not amenable to curative treatment that progressed during prior treatment with anti-PD-1/PD-L1 therapy. Cohort 3A: best response of PD or with SD \<16 weeks, Cohort 3B includes PD1-NSCLC with tumor response or with SD ≥ 16 weeks.

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)

Population: Any Adverse Event a participant has with two or more events in that category is counted only once