Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced the presentation of interim data from a Phase 1B trial (PN001) evaluating MK-3475, an investigational anti-PD-1 immunotherapy, in patients with previously-treated non-small cell lung cancer (NSCLC). The data were presented today by Dr. Edward Garon, Director of Thoracic Oncology, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, at the 15th World Conference on Lung Cancer in Sydney, Australia (Abstract #2416).
Detailed interim data were presented for response rates and safety from a cohort of 38 previously-treated NSCLC patients who received MK-3475 10mg/kg every three weeks as well as initial findings from an analysis of the relationship between response rates and PD-L1 expression.
“We are encouraged by these initial responses in NSCLC patients” said Dr. Eric H. Rubin, vice president, Oncology, MSD Research Laboratories. “Based on these preliminary data and other research, we believe that PD-L1 expression has the potential to be a useful predictor of response to MK-3475 in certain cancers. We look forward to further data from this and other studies to help us to understand the potential role of MK-3475 in lung cancer, and of PD-L1 as a biomarker.”
Based on data from this Phase IB study, MSD initiated a Phase II/III trial comparing two doses of MK-3475, 10mg/kg every three weeks and 2mg/kg every three weeks (10mg/kg Q3W and 2mg/kg Q3W), versus docetaxel in previously-treated patients with NSCLC who have received at least one prior treatment regimen (see clinicaltrials.gov). MSD plans to present data from ongoing studies evaluating 10mg/kgQ2W and 10mg/kgQ3W dosing regimens for MK-3475 in patients with NSCLC in 2014.
Interim results presented at International Association for Study of Lung Cancer 2013 (1)
Tumour responses were assessed by investigator-assessed, immune-related response (irRC) criteria as well as independent, central, blinded radiographic review per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) criteria.
In the 38-patient cohort, the objective response rate in patients receiving MK-3475 was 24 percent based on irRC, and 21 percent based on RECIST (n=33). The median overall survival at time of analysis was 51 weeks with seven of the nine responders, determined by irRC, continuing on treatment. The median response duration has not been reached at the time of this analysis.
The most commonly reported drug-related adverse events in the study, (all grades), were: rash (21%), pruritus (18%), fatigue (16%), diarrhea (13%) and arthralgia (11%). The majority of adverse events were low grade (grade 1-2) there was one incident of grade 3 pulmonary edema.
An analysis of the relationship between PD-L1 expression status and response rates in this NSCLC patient cohort was also presented. Tumour samples were analysed and classified as expressing either zero/low or high levels of PD-L1. High levels of expression according to the assay criteria, were associated with response rates of 67 per cent (6/9) [95% CI; range 30, 93] per irRC and 57 per cent (4/7) [95% CI; range 18, 90] per RECIST. In comparison, tumour samples expressing zero/low levels of PD-L1, according to assay criteria, were associated with response rates of 4 per cent (1/24) [95% CI; range 0, 21] per irRC and 9 per cent (2/22) per RECIST [95% CI; range 1, 29]. Data from more patients are needed to better understand the relationship between PD-L1 expression and response to MK-3475.
Professor Dean Fennell, Chair of Thoracic Medical Oncology, University of Leicester & University Hospitals of Leicester NHS Trust, commented, “These are encouraging Phase 1 results. There is a high unmet need in lung cancer which is a difficult condition to treat with a low survival rate. For lung cancer patients these early results are promising and could signal an even higher response rate when used in previously treated patients with a higher PD-L1 expression.”
(1) Garon E et al. Prelim Clinical Safety and Activity of MK-3475 Monotherapy for the Treatment of Previously Treated Patients with Non-Small Cell Lung Cancer (NSCLC) – IASLC, 15th World Conference on Lung Cancer, 27-30 October, 2013