Study Design
NSCLC, SCLC, pembrolizumab, PAD, toxicity, UC
SCLC, SOLID TUMORS, SMALL CELL LUNG CANCER, PAD, NSCLC
This phase Ib, multicenter, open-label, platform study (ClinicalTrials.gov identifier: NCT02646748) was conducted in the United States. The study evaluated combination of itacitinib or parsaclisib plus pembrolizumab in two parts: Part 1 consisted of Part 1a dose-escalation (enrolling all solid tumors) and Part 1b safety-expansion (focused on selected solid tumors); and Part 2 evaluated parsaclisib plus pembrolizumab in patients with small cell lung cancer (SCLC), NSCLC, and UC (Study design. Note: As of Protocol Amendment 8, enrollment was closed before reaching the planned number of patients. Dose-escalation (Part 1a) was performed using a 3+3 design to evaluate the MTD or pharmacologically active dose (PAD) for itacitinib or parsaclisib, in combination with a fixed dose of pembrolizumab (200 mg intravenously every 3 weeks). The highest dose at which less than one-third of patients experienced a dose-limiting toxicity (DLT) was defined as the MTD. Initial combination doses were based on previous results with itacitinib plus nab-paclitaxel and gemcitabine in advanced solid tumors (In Part 2 (parsaclisib plus pembrolizumab), PD-(L)1 treatment-naïve patients were enrolled and received parsaclisib (0.3 mg once daily) plus pembrolizumab (200 mg every 3 weeks) combination (If pembrolizumab treatment was discontinued, treatment with itacitinib or parsaclisib was also discontinued and the patient entered follow-up. If itacitinib or parsaclisib treatment was discontinued, treatment with pembrolizumab could continue after consultation with the sponsor.