Abstract C122: A randomized, multicenter, open-label, phase 2 study of paclitaxel-carboplatin (PC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus PC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC)
Authors: Spigel David , Luft Alexander , Ramlau Rodryg , Khalil Mazen , Kim Joo-Hang , Mayo Carlos , Depenbrock Henrik , Chao Grace , Obasaju Coleman , Natale Ronald 
Published: May 2016

Abstract
Background: Necitumumab (N) is a 2nd-generation human IgG1 anti-EGFR monoclonal antibody. In a phase 3 trial (SQUIRE) conducted in the first-line setting, N combined with gemcitabine plus cisplatin improved overall survival (OS) in pts with sq-NSCLC compared with chemotherapy alone. PC, another standard of care was selected for this exploratory phase 2 study.
Materials and Methods: Pts with stage IV sq-NSCLC, stratified by ECOG PS (0 vs. 1) and sex (females vs. males) were randomized 2:1and received either PC (P = 200 mg/m2 iv, day 1; C = AUC 6 iv, day 1) plus N (800 mg iv, days 1 and 8) (PC+N arm), or PC alone (PC arm) every 21 days for up to 6 cycles. PC+N pts with a response of stable disease or better continued on N alone until progressive disease or intolerable toxicity. Rash prophylaxis was permitted from the beginning of the trial. The primary endpoint was objective response rate (ORR) based on RECIST 1.1. Secondary endpoints included progression-free survival (PFS), OS, and safety. Sample size and randomization allowed for a 95% confidence interval estimate of ORR for Arm PC+N with a width ≤ 20 percentage points. Final analysis was performed after a minimum of 98 OS events had been observed. No formal hypothesis testing was planned; the study was not powered to show a statistically significant effect for PFS or OS.
Results: 167 pts were randomized (n = 110, PC+N; n = 57, PC). Baseline characteristics were balanced between PC+N and PC, respectively, including males (79% and 77%), ECOG PS 0 (16% and 19%), and PS 1 (85% and 81%). Exposure to chemotherapy was similar in both arms; median dose intensity (DI) for P was 98% vs 95% (PC+N vs PC), and DI for C was 100% vs 95%, respectively, and DI for N was 96%. 53% of PC+N pts continued N alone for a median of 4 additional cycles (range 2.0-7.5). The addition of N to PC resulted in an ORR of 48.9% vs 40.0%. Disease control rate was 87.2% vs 84.0% in PC. PFS HR was 1.0 (mPFS 5.4 vs 5.6 months). Median OS was 13.2 vs 11.2 months (HR = 0.83, p = 0.379). There was a higher rate of events for the PC+N arm during the first 4 months, with a later trend toward improved survival after 4 months. Most frequently reported SAEs were pneumonia (12.3% vs. 5.5%) and febrile neutropenia (5.7% vs. 3.6%). Grade ≥3 AEs typically associated with EGFR mAbs that showed a &gt;2% increase were hypomagnesemia (5.7% vs 0) and rash (2.8% vs 0). Any grade venous thromboembolic events occurred in 3.8% of patients in the PC+N group vs 3.6% of patients in the PC group. Infusion related reactions of any grade occurred in 3.8% of patients in the PC+N group vs 9.1% in the PC group.
Conclusions: The addition of N to PC resulted in an increased ORR compared to PC alone, indicating an add-on effect. The lower incidence of grade 3 rash observed here (2.8%) versus SQUIRE (7%) may be due to the permission of first cycle rash prophylaxis (SQUIRE no rash prophylaxis permitted prior to cycle 2). The safety profile in this study is consistent with the expected safety profile of an EGFR mAb administered in this combination in the sq-NSCLC population. Clinical trial information: NCT01769391.
Citation Format: David Spigel, Alexander Luft, Rodryg Ramlau, Mazen Khalil, Joo-Hang Kim, Carlos Mayo, Henrik Depenbrock, Grace Chao, Coleman Obasaju, Ronald Natale. A randomized, multicenter, open-label, phase 2 study of paclitaxel-carboplatin (PC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus PC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C122.