APX005M With Nivolumab and Cabiralizumab in Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma

Inclusion Criteria: Must have one of the following diagnoses: Melanoma: Unresectable stage III or stage IV melanoma, irrespective of BRAF status, with histologic or cytologic confirmation. RCC: Histologic or cytologically documented, locally advanced unresectable or metastatic RCC irrespective of histologic subtype NSCLC: Histologic or cytologically documented, locally advanced or metastatic (i.e. Stage IIIB not eligible for definitive chemoradiotherapy, stage IV, or recurrent) NSCLC. Patients known to harbor an ALK rearrangement or EGFR mutation known to be sensitive to FDA-approved tyrosine kinase inhibitors (TKI), are only eligible after experiencing disease progression (during or after treatment) or intolerance to an FDA approved ALK TKI or EGFR TKI, respectively. Patients with TKI-treated EGFR mutant NSCLC harboring the secondary EGFR T790M tumor must have received prior osimertinib. Patients with crizotinib-treated ALK rearranged NSCLC must have received a next generation ALK inhibitor. Additional Inclusion Criteria: 1. Biopsy proven metastatic melanoma, NSCLC or RCC whose disease has progressed on a prior regimen containing a PD-1 or PD-L1 inhibitor, without intervening therapy. 2. At least 1 site of disease must be accessible to provide repeat biopsies for tumor tissue. This site may be a target lesion as long as it will not be made unmeasurable by the biopsy procedure. 3. Age ≥18, able to understand and sign the informed consent form. 4. ECOG performance status \< 2. 5. Any number of previous treatments. Other prior systemic therapies must have been administered at least 4 weeks before administration of the study drugs; the exception to this is small molecule inhibitors, which must be stopped at least 2 weeks or after five half-lives of the drug, whichever is shorter, prior to the start of the study drugs. 6. Life expectancy of at least 6 months. 7. A history of previously treated brain metastases is allowed, provided that they are stable for at least 4 weeks. 8. Willingness to undergo mandatory tumor biopsy prior to initiation of therapy and before the fifth cycle. 9. Willingness to provide an archival specimen block, if available, for research. 10. Patients must have normal organ and marrow function (as outlined in Section 3.2.2). 11. Female subject of childbearing potential should have a negative urine or serum pregnancy within 24 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 12. Female subjects of childbearing potential should be willing to use a highly effective contraception (hormonal or IUD) or be surgically sterile, or abstain from heterosexual activity for a period of at least 5 months after the last dose of study drug. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. 13. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through at least 7 months after the last dose of study drug. 14. Patients must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST v1.1 criteria. a. Tumor sites situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are not considered measurable unless there has been demonstrated progression in the lesion. Sites for biopsy must be distinct from target lesions used for efficacy assessment. 15. Prior focal radiotherapy is allowed. Radiation to brain, pulmonary or intestinal sites must be completed at least 4 weeks prior to study Day 1. There is no time restriction prior to study Day 1 for patients who have received radiation to bone, soft tissue or other sites. No radiopharmaceuticals (strontium, samarium) within 8 weeks before first dose of study drug administration. 16. Prior surgery that requires general anesthesia must be completed at least 1 week before first dose of study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before first dose of study drug administration and patients should have recovered. Exclusion Criteria: 1. Untreated brain metastases. 2. A patient who has had prior immune therapy or chemotherapy, within 4 weeks prior to study Day 1, or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent will be excluded. The exception is targeted therapy that must have been completed at least 2 weeks or after 5 half-lives, which ever is shorter, prior to study Day 1. Patients who have had prior ipilimumab must have received their last dose no less than 4 weeks prior to study Day 1. 1. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 2. Note: Toxicity that has not recovered to ≤ Grade 1 is allowed if it meets the inclusion requirements for laboratory parameters. 3. Has had prior treatment with any other CSF1R inhibitor or CD40 agonist 4. Use of corticosteroids to control immune related adverse events at enrollment will not be allowed, and patients who previously required corticosteroids for symptom control must be off steroids for at least 2 weeks. Low-dose steroid use (≤10 mg of prednisone or equivalent) as corticosteroid replacement therapy for primary or secondary adrenal insufficiency is allowed. 5. Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to prior treatments with the exception of clinically insignificant adverse events such as alopecia, clinically insignificant laboratory abnormalities, clinically insignificant rash and Grade 2 neuropathy. 6. History of grade 3-4 neurologic or cardiac toxicity or life-threatening liver toxicity poorly responsive to steroids with prior anti-PD-1/anti-PDL1 monotherapy. 7. Presence of leptomeningeal disease. 8. Has active autoimmune disease unrelated to use of immune checkpoint inhibitors that has required systemic treatment in the past year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 9. Pregnancy or breast feeding. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab, cabiralizumab or APX005M, breastfeeding must be discontinued if the mother is enrolled on this trial. 10. Patients may not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment. 11. Either a concurrent condition (including medical illness, such as active infection requiring treatment with intravenous antibiotics or the presence of laboratory abnormalities) or history of a prior condition that places the patient at unacceptable risk if he/she were treated with the study drug or a medical condition that confounds the ability to interpret data from the study. 12. Concurrent, active malignancies in addition to those being studied. 13. Active (non-infectious) pneumonitis. 14. Has a known Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), or Hepatitis C (HCV) acute or chronic infection. 15. Has received a live vaccine within 30 days prior to the first dose of trial treatment. 16. History of myocardial infarction or unstable angina within 3 months prior to Cycle 1, Day 1. 17. Prisoners, or subjects who are under compulsory detention 18. Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels 19. History of anti-drug antibodies, severe allergic, anaphylactic, or other infusion-related reaction to a previous biologic agent 20. Concomitant use of statins while on study. However, a patient using statins for over 3 months prior to study drug administration and in stable status without CK rise may be permitted to enroll 21. Open wounds and active skin infections 22. Uveal melanoma in the Phase Ib dose expansion trial