CD40 Agonistic Antibody APX005M in Combination With Nivolumab

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

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 had
confirmed progressive disease during treatment with anti-PD-1/PD-L1 therapy. 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.