Safety and clinical activity of MK-3475 as initial therapy in patients with advanced non-small cell lung cancer (NSCLC).
Lung Cancer - Non-Small Cell Metastatic
Lung Cancer - Non-Small Cell Metastatic
2014 ASCO Annual Meeting
J Clin Oncol 32:5s, 2014 (suppl; abstr 8007)
2014 ASCO Annual Meeting!
Session: Lung Cancer - Non-small Cell Metastatic
Type: Oral Abstract Session
Time: Monday June 2, 3:00 PM to 6:00 PM
Location: E Hall D2
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Author(s): Naiyer A. Rizvi, Edward B. Garon, Amita Patnaik, Leena Gandhi, Natasha B. Leighl, Ani Sarkis Balmanoukian, Jonathan Wade Goldman, Joseph Paul Eder, Elizabeth Johnson, George R. Blumenschein, Matthew A. Gubens, Kyriakos P. Papadopoulos, Gregory M. Lubiniecki, Jin Zhang, Michelle Niewood, Kenneth Emancipator, Marisa Dolled-Filhart, Mary Elizabeth Hanson, Rina Hui; Memorial Sloan Kettering Cancer Center, New York, NY; University of California, Los Angeles, Los Angeles, CA; START Center for Cancer Care, San Antonio, TX; Dana-Farber Cancer Institute, Boston, MA; Princess Margaret Cancer Centre, Toronto, ON, Canada; The Angeles Clinic and Research Institute, Los Angeles, CA; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; AstraZeneca, Waltham, MA; Mayo Clinic, Jacksonville, FL; Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; University of California, San Francisco, San Francisco, CA; Merck & Co., Inc., Whitehouse Station, NJ; Westmead Hospital, University of Sydney, Sydney, Australia
Background: Programmed death-1 (PD-1) receptor-ligand interaction inhibits T cell activation against tumor cells. MK-3475 is a potent and highly selective humanized monoclonal antibody against PD-1 designed to directly block its interaction with its ligands, PD-L1 and PD-L2, thus removing the inhibition of T cell activation against cancer. MK-3475 led to prolonged anti-tumor activity in previously treated NSCLC patients. This Phase I study evaluated the safety, tolerability, and clinical activity of MK-3475 as initial therapy in patients with locally advanced or metastatic NSCLC. Methods: Patients with no prior systemic therapy for metastatic disease whose tumors expressed PD-L1 by a preliminary immunohistochemical assay were randomized to MK-3475 10 mg/kg every 2 or 3 wks (Q3W). The first 11 patients were randomized to 2 mg/kg and 10 mg/kg Q3W. At least 1 measurable tumor lesion, ECOG performance status of 0 to 1, adequate organ function and adequate tumor biopsy were required for enrollment. Prior adjuvant therapy was allowed if it preceded relapse by at least a year. Tumor response was assessed every 9 weeks until confirmed disease progression per immune related response criteria (irRC; investigator review); RECIST 1.1 by independent central review will also be performed. Results: 84 patients submitted tissue for PD-L1 assessment and 57 patients had tumors that expressed PD-L1. Between Feb 2013 and Oct 2013, 45 patients started treatment (n=6 2Q3W, n=23 10Q3W, n=16 10Q2W). Preliminary data indicate an ORR (confirmed and unconfirmed) of 36% (67% 2 mg/kg Q3W, 27% 10 mg/kg Q3W, 35% 10 mg/kg Q2W) by irRC. 25 patients (55%), including all but 2 responders, remain on treatment (treatment duration from 12+ to 48+ wks). 52% of patients experienced a drug-related adverse event (AE), usually grade 1-2 in severity, most commonly fatigue (14%), pruritus (8%), dermatitis acneiform (6%), diarrhea (6%) and dyspnea (6%). There was a single drug-related grade 3-5 AE, a grade 3 pericardial effusion. Conclusions: These data suggest that MK-3475 is generally well-tolerated and provides robust antitumor activity in a first-line setting in patients with locally advanced or metastatic NSCLC that expresses PD-L1. Clinical trial information: NCT01295827.
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