Abstract CT141: Phase I study of nivolumab (nivo) + nab-paclitaxel (nab-P) + carboplatin (C) in advanced NSCLC: safety and efficacy results
Authors: Waterhouse David M. , George Ben , Gutierrez Martin , Otterson Greg A. , Ko Amy , Ong Teng Jin , Stergiopoulos Sotirios , Trunova Nataliya , Kelly Karen 
Published: July 2016

Abstract
Background: Chemotherapy leads to tumor lysis and release of tumor antigens, which may prime the immune system for checkpoint inhibitors. The combination of a taxane + immune checkpoint inhibitor has been reported to improve response in non-small cell lung cancer (NSCLC; Giaccone et al. ESMO 2015 [abstract 247]). This analysis provides interim results from the first of the 2 lung cohorts of a phase I study of nivo with the standard dose and schedule of nab-P/C.
Methods: The 2 lung cohorts (Arms C and D) were initiated sequentially in part 1 of the study. In Arm C, patients (pts) with stage IIIB/IV NSCLC and no prior chemotherapy for metastatic disease received 4 cycles of nab-P 100 mg/m2 on days 1, 8, and 15 + C area under the curve 6 on day 1 of a 21-day cycle in combination with nivo 5 mg/kg on day 15 starting at cycle 1. Nivo was continued as monotherapy at cycle 5. The same regimen was administered in Arm D, with nivo starting at cycle 3.The primary objective of part 1 was the number of dose-limiting toxicities (DLTs) in each treatment arm, including grade 3/4 treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. Pts treated with ? 2 cycles of nivo + nab-P/C or who discontinued due to DLT after the start of nivo and prior to completing 2 cycles of nivo + nab-P/C were considered DLT evaluable. If deemed safe per DLT evaluation, the treatment arms may be expanded to further assess safety, tolerability, and antitumor activity.
Results: As of Nov 9, 2015, 12 pts had been enrolled in Arm C; of these, 9 received nivo + nab-P/C before the data cut off date. Overall, most pts were aged ? 65 years (67%) and female (58%); 58% had adenocarcinoma, and 42% had squamous cell carcinoma. No DLTs were observed. The most frequent grade ? 3 TEAEs common to all treated pts and, separately, those treated with nivo + nab-P/C were neutropenia (25% and 22%) and hypokalemia (17% and 22%, 2 out of 3 pts had history of thyroid disorder). No pneumonitis has been reported to date. Of the 9 nivo-treated, response evaluable pts, 6 had a partial response, and 3 had stable disease (SD). In pts not receiving nivo, 1 patient had SD. Overall tumor burden decrease from baseline in total length of target lesions of responding pts ranged from 31% to 83%. Two pts discontinued treatment prior to nivo administration (1 due to AEs and 1 due to voluntary withdrawal); 1 additional pt received nivo after the data cut off date. One pt discontinued due to progression after 23 weeks of nivo + nab-P/C. No treatment-related deaths have been reported to date.
Conclusions: In Arm C of the lung cancer cohort, the addition of nivo on day 15 to the standard dose and schedule of nab-P/C did not appear to result in added toxicity or raise new safety/tolerability concerns. Preliminary assessments of antitumor activity were encouraging. Expansion of this treatment arm to further assess safety and tolerability is underway and will be updated (NCT02309177).
Citation Format: David M. Waterhouse, Ben George, Martin Gutierrez, Greg A. Otterson, Amy Ko, Teng Jin Ong, Sotirios Stergiopoulos, Nataliya Trunova, Karen Kelly. Phase I study of nivolumab (nivo) + nab-paclitaxel (nab-P) + carboplatin (C) in advanced NSCLC: safety and efficacy results. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT141.