Presentation Abstract

Abstract Number: CT105
Presentation Title: MK-3475 (anti-PD-1 monoclonal antibody) for non-small cell lung cancer (NSCLC): Antitumor activity and association with tumor PD-L1 expression
Presentation Time: Sunday, Apr 06, 2014, 4:35 PM - 4:55 PM
Location: Ballroom 20A-C, San Diego Convention Center
Author Block: Leena Gandhi1, Ani Balmanoukian2, Rina Hui3, Omid Hamid2, Naiyer A. Rizvi4, Natasha Leighl5, Matthew Gubens6, Jonathan W. Goldman7, Gregory M. Lubiniecki8, Kenneth Emancipator9, Marisa Dolled-Filhart9, Jared K. Lunceford9, Michelle Niewood10, Kevin Gergich8, Edward B. Garon11. 1Dana-Farber Cancer Institute, Boston, MA; 2The Angeles Clinic and Research Institute, Los Angeles, CA; 3Westmead Hospital, Sydney, Australia; 4Memorial Sloan-Kettering Cancer Center, New York, NY; 5Princess Margaret Hospital, Toronto, ON, Canada; 6University of California, San Francisco, San Francisco, CA; 7UCLA, Santa Monica, CA; 8Merck & Co., Inc., North Wales, PA; 9Merck & Co., Inc., Rahway, NJ; 10Merck & Co., Inc., Philadelphia, PA; 11David Geffen School of Medicine at UCLA, Los Angeles, CA
Abstract Body: 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 IHC
PD-L1 Tumor
N for irRCORR by irRC, n (%),
[95% CI]
N for RECISTORR by RECIST, n (%),
[95% CI]
PFS rate* at
6 months
(95% CI)
PFS StatisticsOS rate^ at
6 months
(95% CI)
OS Statistics
High (score ≥ potential cut point)96 (67%), [30%, 93%]74 (57%), [18%, 90%]67% (42%-100%)Median: not reached89% (71%-100%)Median: not reached
Low (score < potential cut point)220 (0%), [0%, 15%]201 (5%),# [0%, 25%]11% (3%-40%)Median: 2.1 months33% (18%-62%)Median: 3.9 months
HR (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)
_<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.