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:

• 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.
• 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.
• Age ≥18, able to understand and sign the informed consent form.
• ECOG performance status 1 year.
• 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.
• 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.

• 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.
• 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

• Untreated brain metastases.
• 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.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Note: Toxicity that has not recovered to ≤ Grade 1 is allowed if it meets the inclusion requirements for laboratory parameters.
• Has had prior treatment with any other CSF1R inhibitor or CD40 agonist
• 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 pr