The ongoing annual AACR meeting this week included some fairly encouraging clinical trial news for treatment of pleural mesothelioma. One portion of the news arises from a 25 person clinical trial at the University of Pennsylvania. Of those 25 persons, 28% (7) obtained an apparent regression of the tumor and another 48% (12) obtained “stable disease.” The treatment involves a PD-1 inhibitor, which is one of the current “hot” treatments in the world of cancer therapy. The goal of the drug is to alter the workings of so-called “checkpoint inhibitors.” Said in a positive way, the goal is to further immune system attention to the tumor by “releasing a brake” on the immune system. Many similar PD-1 clinical trials are underway for other solid tumors. For a detailed, open access medical journal article, see Dolan, PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy, Cancer Control, 2014 Jul;21(3):231-7.
Set out below is the pertinent portion of Merck’s press release:
“KEYTRUDA Demonstrated 28 Percent Overall Response Rate and 76 Percent Disease Control Rate in Difficult-to-Treat Cancer
First Findings from KEYNOTE-028, Merck’s Innovative Basket Trial in 20 Cancers
April 19, 2015 12:45 PM Eastern Daylight Time
PHILADELPHIA–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentation of data investigating the use of KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, in 25 patients with advanced pleural mesothelioma, a difficult-to-treat cancer of the lining of the lungs, abdomen and other organs. The early findings presented showed an overall response rate (confirmed and unconfirmed) of 28 percent with KEYTRUDA in patients with tumors that expressed PD-L1. Additionally, 48 percent of patients had stable disease, resulting in a disease control rate of 76 percent. These data, from KEYNOTE-028, will be presented today at the American Association for Cancer Research (AACR) Annual Meeting by Dr. Evan Alley, Abramson Cancer Center, University of Pennsylvania, and were part of the AACR official press program (abstract #CT103). This is the first data to be presented from KEYNOTE-028, Merck’s innovative basket trial designed to evaluate the efficacy and safety of KEYTRUDA in patients with 20 difficult-to-treat cancers.
“This presentation at AACR marks the first time that data involving an anti-PD-1 therapy have been presented in pleural mesothelioma, which is a rare, hard-to-treat cancer with very limited treatment options”
“This presentation at AACR marks the first time that data involving an anti-PD-1 therapy have been presented in pleural mesothelioma, which is a rare, hard-to-treat cancer with very limited treatment options,” said Dr. Alley, clinical associate professor of medicine, Abramson Cancer Center. “While early, the disease control rates observed in this study are very encouraging, and indicate that further study is warranted to evaluate the potential role of KEYTRUDA in the treatment of malignant pleural mesothelioma.”
“This unique study is helping to accelerate our understanding of where KEYTRUDA may work in cancers with limited or no treatment options,” said Dr. Roger Dansey, therapeutic area head and senior vice president, oncology late stage development, Merck Research Laboratories. “These early data in advanced pleural mesothelioma reinforce the clinically meaningful results we are seeing with KEYTRUDA across multiple cancers.”
At the time of the analysis, 40 percent of patients (n=10/25) remained on treatment. Adverse events in the study were consistent with previously reported safety data for KEYTRUDA. The most common treatment-related adverse events (occurring in greater than twenty percent of patients) were fatigue (24%) and nausea (24%). Two Grade 3 treatment-related adverse events occurred: ALT increased (n=1) and thrombocytopenia (n=1). Some patients experienced adverse events of special interest, including rash (n=4), ALT/AST increased (n=1), hypersensitivity (n=1) and iridocyclitis (n=1); two required a dose interruption (one because of ALT/AST increased, one because of iridocyclitis). No patients discontinued as a result of treatment-related adverse events, and there were no treatment-related deaths.
About the KEYNOTE-028 Study
KEYNOTE-028 is an ongoing, multi-cohort, non-randomized Phase 1b basket trial evaluating the safety, tolerability, and anti-tumor activity of KEYTRUDA monotherapy (10 mg/kg dosed every two weeks) in 320 patients with PD-L1 positive advanced solid tumors that have not responded to current therapy or for which current therapy is not appropriate.
About KEYTRUDA® (pembrolizumab)
KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.
KEYTRUDA is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Merck is advancing a broad and fast-growing clinical development program for KEYTRUDA with more than 85 clinical trials – across more than 30 tumor types and over 14,000 patients – both as a monotherapy and in combination with other therapies.”