Abstract CT105: MK-3475 (anti-PD-1 monoclonal antibody) for non-small cell lung cancer (NSCLC): Antitumor activity and association with tumor PD-L1 expression
Authors: Gandhi Leena , Balmanoukian Ani , Hui Rina , Hamid Omid , Rizvi Naiyer A. , Leighl Natasha , Gubens Matthew , Goldman Jonathan W. , Lubiniecki Gregory M. , Emancipator Kenneth , Dolled-Filhart Marisa , Lunceford Jared K. , Niewood Michelle , Gergich Kevin , Garon Edward B. 
Published: May 2015

Abstract
Background: MK-3475, a humanized monoclonal IgG4 antibody against PD-1, has demonstrated durable antitumor activity in NSCLC and melanoma. Preliminary data presented at the 2013 World Congress of Lung Cancer showed a relationship between tumor PD-L1 expression and overall response to MK-3475. Here, we present updated data on tumor PD-L1 expression and its relationship with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Methods: In a phase I study, 38 previously treated NSCLC patients received MK-3475 10 mg/kg Q3W. Tumor response was assessed every 9 weeks by immune-related response criteria (irRC) per investigator review and by RECIST v1.1 per independent radiologic review. A new tumor biopsy performed within 60 days prior to the first dose of MK-3475 was required. Tumor PD-L1 expression was assessed by IHC. A potential cut point for PD-L1 expression was determined by the Youden Index from a receiver operating characterstics curve developed from the investigators’ irRC assessments.
Results: Confirmed ORR for the entire cohort of 38 patients per investigators’ irRC assessments was 24%, median PFS was 9 weeks, and median OS was 51 weeks. PD-L1 IHC score was above a potential cut point in 9 patients and below a potential cut point in 22 patients; tumor was not submitted for or staining was not evaluable in 7 patients. Significant associations between tumor PD-L1 expression and ORR, PFS, and OS were observed (Table).
Conclusions: Tumor PD-L1 expression levels were associated with tumor response, PFS, and OS in patients with NSCLC treated with MK-3475. The preliminary finding of minimal anti-tumor activity in patients whose tumors express low levels of PD-L1 suggests that PD-L1 is an important biomarker for patients with NSCLC treated with MK-3475.
Relationship of PD-L1 expression and activity in tumor biopsies evaluable by IHCPD-L1 TumorExpressionN for irRCORR by irRC, n (%),[95% CI]N for RECISTORR by RECIST, n (%),[95% CI]PFS rate* at6 months(95% CI)PFS StatisticsOS rate^ at6 months(95% CI)OS StatisticsHigh (score ≥ potential cut point)96 (67%), [30%, 93%]74 (57%), [18%, 90%]67% (42%-100%)Median: not reached89% (71%-100%)Median: not reachedLow (score &lt; potential cut point)220 (0%), [0%, 15%]201 (5%),# [0%, 25%]11% (3%-40%)Median: 2.1 months33% (18%-62%)Median: 3.9 monthsHR (95% CI) for high vs low PD-L1 expression_____0.22 (0.07-0.67)_0.32 (0.10-0.99)One-sided P value(PD-L1 association test)_&lt;0.001 (Fisher's exact test)__0.009 (Fisher's exact test)0.004 (Cox regression)_0.024 (Cox regression)*Based on investigators' irRC assessments.#Response was not confirmed.^Based on the 31 patients with evaluable tumor.
Citation Format: Leena Gandhi, Ani Balmanoukian, Rina Hui, Omid Hamid, Naiyer A. Rizvi, Natasha Leighl, Matthew Gubens, Jonathan W. Goldman, Gregory M. Lubiniecki, Kenneth Emancipator, Marisa Dolled-Filhart, Jared K. Lunceford, Michelle Niewood, Kevin Gergich, Edward B. Garon. MK-3475 (anti-PD-1 monoclonal antibody) for non-small cell lung cancer (NSCLC): Antitumor activity and association with tumor PD-L1 expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT105. doi:10.1158/1538-7445.AM2014-CT105