P3.02c-056 Interim Results From the Phase I Study of Nivolumab + nab-Paclitaxel + Carboplatin in Non-Small Cell Lung Cancer (NSCLC): Topic: IT

Abstract

Chemotherapy, including nab-paclitaxel, plus an immune checkpoint inhibitor has demonstrated antitumor activity in patients with metastatic breast cancer (mBC) and NSCLC. Here, results from the 2 lung cohorts of the phase I nivolumab + nab-paclitaxel in pancreatic cancer (± gemcitabine), NSCLC (+ carboplatin), and mBC safety trial are presented. Enrollment in the lung cohorts (C and D) was initiated in two sequential parts: Dose-limiting toxicity (DLT) evaluation was done in Part 1 prior to treatment arm expansion in Part 2. Chemotherapy-naive patients with stage IIIB/IV NSCLC received 4 cycles of nab-paclitaxel 100 mg/m2 D 1, 8, 15 + carboplatin area under the curve (AUC) 6 D 1 + nivolumab 5 mg/kg D 15 (starting in cycle 1 [Arm C] or cycle 3 [Arm D]) of each 21-day cycle; nivolumab continued as monotherapy from cycle 5. Primary endpoints were DLTs (Part 1), and grade 3/4 treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation (Parts 1 and 2). Patients who received ≥ 2 nivolumab cycles and remained on study for 14 days after the last nivolumab dose or discontinued due to DLT prior to completing 2 nivolumab cycles were considered DLT-evaluable. Key secondary endpoints include safety, PFS, OS, and ORR. As of May 25, 2016, 21 patients have enrolled in Arm C (18 nivolumab-treated); most were aged ≥ 65 years (57.1%) and female (71.4%), 33.3% had ECOG PS 0, 42.9% and 33.3% had adenocarcinoma and squamous cell carcinoma, respectively. No DLTs were reported (5 DLT-evaluable patients). The most common grade 3/4 AEs in Arm C (all patients) were neutropenia (28.6%), anemia (19.0%), and hypokalemia (14.3%); gastrointestinal disorders (11.1%) were the most frequent grade 3/4 immune-related AE in nivolumab-treated pts. Seven patients (5 nivolumab-treated) discontinued treatment (majority due to progressive disease [PD]). Of the 18 nivolumab-treated patients, 9 had a PR, 8 had stable disease, and data is pending in 1 patient; tumor shrinkage (baseline to nadir) ranged from 3% to 83%. The median PFS (n = 4 with PD or death; nivolumab-treated) was 7.3 months (treatment duration, 0.7 - 9.4 months). Eight patients have enrolled in Arm D (4 nivolumab-treated); 1 DLT (pneumonitis) was reported in 4 DLT-evaluable patients. These results demonstrate that the combination of nivolumab with nab-paclitaxel/carboplatin is tolerable and has promising antitumor activity in patients with NSCLC. Updated results will be presented at the meeting. (NCT02309177).