This trial is a phase 1/1b study to evaluate the safety, efficacy, and tolerability of APX005M in combination with nivolumab and cabiralizumab. The phase 1 dose escalation portion of the study will enroll patients with advanced solid tumors melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) in 6 cohorts to determine the recommended phase II dose (RP2D) of APX005M. The phase 1b dose expansion portion will study the triple drug combination separately in the three disease cohorts: melanoma, NSCLC, and RCC. Submitted on 3/29/2018; investigational new drug (IND) number is pending and will be added to the record once received.
Name: APX005M
Name: Cabiralizumab
Name: Nivolumab
Description: AEs and SAEs will be examined with (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.03
Measure: Safety and Tolerability measured by assessing serious adverse events (SAEs)and adverse events (AEs) Time: From study enrollment up to 12 months.Description: This 5-point scale ranges from full functioning (1) to dead (5)
Measure: Safety and Tolerability measured by Eastern Cooperative Oncology Group(ECOG) performance status Time: From study enrollment up to 12 months.Description: ORR will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v. 1.1.
Measure: Efficacy measured by objective response rate (ORR) Time: Six months.Description: This outcome will be assessed by blood collection.
Measure: Pharmacokinetics (PK) of APX005M assessed by area under the curve (AUC). Time: 12 weeksDescription: This outcome will be assessed by blood collection.
Measure: Pharmacokinetics (PK) of APX005M assessed by minimum blood plasma concentration (Cmin). Time: 12 weeksDescription: This outcome will be assessed by blood collection.
Measure: Pharmacokinetics (PK) of APX005M assessed by clearance (CL). Time: 12 weeksDescription: This outcome will be assessed by blood collection.
Measure: Pharmacokinetics (PK) of APX005M assessed by volume of distribution (Vss) Time: 12 weeksDescription: This outcome will be assessed by blood collection.
Measure: Pharmacokinetics (PK) of APX005M assessed by peak plasma concentration (Cmax). Time: 12 weeksDescription: This outcome will be assessed with tissue biopsies.
Measure: Tissue-based pharmacodynamics (PD) of APX005M, in combination with nivolumab and cabiralizumab assessed by CD8+ T cells . Time: Change from baseline to 8 weeks.Description: This outcome will be assessed with tissue biopsies.
Measure: Tissue-based pharmacodynamics (PD) of APX005M, in combination with nivolumab and cabiralizumab assessed by CD163+ macrophages . Time: Change from baseline to 8 weeks.Description: This outcome will be assessed via blood collection.
Measure: Blood-based pharmacodynamics (PD) of APX005M, in combination with nivolumab and cabiralizumab assessed by circulating CD163+ macrophages . Time: Change from baseline to 8 weeks.Description: This outcome will be assessed via blood collection.
Measure: Blood-based pharmacodynamics (PD) of APX005M, in combination with nivolumab and cabiralizumab assessed by circulating CD8+ T cells. Time: Change from baseline to 8 weeks.Description: This outcome will be assessed via blood collection.
Measure: Cytokine-based pharmacodynamic (PD) biomarkers of APX005M, in combination with nivolumab and cabiralizumab assessed by CD40L levels. Time: Change from baseline to 8 weeks.Description: This outcome will be assessed via blood collection.
Measure: Cytokine-based pharmacodynamic (PD) biomarkers of APX005M, in combination with nivolumab and cabiralizumab assessed by IL-10 levels. Time: Change from baseline to 8 weeks.Description: This outcome will be assessed via blood collection.
Measure: Cytokine-based pharmacodynamic (PD) biomarkers of APX005M, in combination with nivolumab and cabiralizumab assessed by interferon-gamma levels . Time: Change from baseline to 8 weeks.Description: PFS will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v. 1.1.
Measure: Efficacy measured by progression-free survival (PFS) Time: From study enrollment up to 6 years.Description: OS will be ascertained by review of the National Death Index, medical records and follow-up phone calls.
Measure: Efficacy measured by overall survival (OS) Time: From study enrollment up to 6 years.Allocation: Non-Randomized
Single Group Assignment
There is one SNP
Patients with TKI-treated EGFR mutant NSCLC harboring the secondary EGFR T790M tumor must have received prior osimertinib. --- T790M ---