Clinical efficacy and safety of lambrolizumab (MK-3475, Anti-PD-1 monoclonal antibody) in patients with advanced melanoma.

Melanoma/Skin Cancers
Session Type and Session Title: 
Clinical Science Symposium, PD1/PDL1: An Effective Target in Melanoma
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 9009)
Antoni Ribas, Caroline Robert, Adil Daud, F. Stephen Hodi, Jedd D. Wolchok, Richard Kefford, Amita Patnaik, Wen-Jen Hwu, Jeffrey S. Weber, Anthony Joshua, Peter Hersey, Tara C. Gangadhar, Richard Wayne Joseph, Roxana Stefania Dronca, Hassane M. Zarour, Scot Ebbinghaus, Kevin Gergich, Xiaoyun (Nicole) Li, Soonmo Peter Kang, Omid Hamid; Med-Hematology & Oncology, University of California, Los Angeles, Los Angeles, CA; Institut Gustave Roussy, Villejuif, France; University of California, San Francisco, San Francisco, CA; Dana-Farber Cancer Institute, Boston, MA; Memorial Sloan-Kettering Cancer Center, New York, NY; Westmead Hospital and Melanoma Institute Australia, University of Sydney, Sydney, Australia; START Center for Cancer Care, San Antonio, TX; The University of Texas MD Anderson Cancer Center, Houston, TX; Moffitt Cancer Center, Comprehensive Melanoma Research Center, Tampa, FL; Princess Margaret Cancer Center, Toronto, ON, Canada; Calvary Mater Newcastle, Waratah, Australia; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; Mayo Clinic Cancer Center, Jacksonville, FL; Mayo Clinic, Department of Medical Oncology, Rochester, MN; University of Pittsburgh Cancer Institute, Pittsburgh, PA; Merck & Co, Inc, North Wales, PA; Merck & Co, Inc, Rahway, NJ; The Angeles Clinic and Research Institute, Los Angeles, CA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Programmed death-1 (PD-1) is an inhibitory T-cell co-receptor that may lead to suppression of antitumor immunity. Lambrolizumab is a humanized monoclonal IgG4 antibody against PD-1. This study explored the safety and clinical activity of lambrolizumab in patients (pts) with advanced melanoma (MEL). Methods: In this ongoing phase 1b expansion study of MEL pts with or without previous ipilimumab (IPI) treatment, lambrolizumab was administered IV every 2 or 3 weeks until disease progression or unacceptable toxicity. Tumor response was assessed every 12 weeks by independent, central, blinded radiographic review per immune-related response criteria and RECIST 1.1. Results: As of December 1, 2012, 294 pts with MEL were enrolled, including 179 IPI-naive and 115 IPI-pretreated. Pts received lambrolizumab 10 mg/kg (n = 183) or 2 mg/kg (n = 111). Preliminary data from the first 85 consecutive pts dosed before April 25, 2012, who had independent radiologic review available as of December 3, 2012, indicate a confirmed overall response rate per RECIST 1.1 of greater than 35%, pooled across all doses and schedules and including both IPI-naive and IPI-pretreated patients. The median duration of response has not been reached as only 2 pts who had initial response discontinued due to disease progression, but the duration of confirmed responses range from 28+ to 240+ days (up to 8+ months). Among 133 pts who were dosed with lambrolizumab before July 31, 2012, and evaluable for adverse events (AEs) as of September 28, 2012, fatigue (22%), rash (18%), and pruritus (14%) were the most common drug-related AEs (mostly grade 1/2). The incidence of drug-related grade 3/4 AEs was 10% (24% regardless of attribution). Four drug-related cases of pneumonitis were reported, all of grade 1/2. Grade 3/4 drug-related hypothyroidism (n = 1) and hyperthyroidism (n = 1) were noted. Conclusions: Preliminary data suggest that lambrolizumab has significant antitumor activity and is well tolerated with manageable side effects in both IPI-naive and IPI-pretreated MEL pts. These data have led to an ongoing, international, randomized study of lambrolizumab versus chemotherapy in IPI-pretreated MEL. Clinical trial information: NCT01295827.