MSD, known as Merck in the United States and Canada, announced the first presentation of data on the investigational use of pembrolizumab – the company’s anti-PD-1 therapy – in PD-L1 positive, advanced gastric cancer.
MSD, known as Merck in the United States and Canada, announced the first presentation of data on the investigational use of pembrolizumab – the company’s anti-PD-1 therapy – in PD-L1 positive, advanced gastric cancer.
The early findings presented showed an overall response rate (confirmed and unconfirmed) of 31 percent with pembrolizumab as monotherapy, as measured by investigator assessed, RECIST v1.1 (n= 12/39: 95% CI, 17-47.6). (1) Similar overall response rates were observed in Asian patients (a population with a high incidence of gastric cancer) and non-Asian patients. At the time of analysis, response durations ranged from 8+ to 20+ weeks with 11 of 12 responders continuing on therapy. (1)
These data, from a cohort of the ongoing Phase 1b KEYNOTE-012 study, were presented, as part of a late-breaking abstract oral session, by Dr. Kei Muro, Aichi Cancer Center Hospital, Nagoya, Japan, at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain (ABSTRACT #LBA15). Data investigating the use of pembrolizumab monotherapy in five tumour types will be presented at ESMO 2014.
“MSD is advancing the development of pembrolizumab across different tumour types and lines of therapy,” said Dr. Alise Reicin, vice president, oncology, Merck Research Laboratories. “We are encouraged by the signals of anti-tumour activity in advanced gastric cancer, and are eager to move ahead with the Phase 2 study to better understand the potential of pembrolizumab in advanced gastric cancer.”
Early findings for investigational use of pembrolizumab in advanced gastric cancer
Data from a cohort of the ongoing Phase 1b KEYNOTE-012 study evaluated pembrolizumab monotherapy at 10 mg/kg every two weeks in patients with advanced gastric cancer whose tumours were determined to be positive for PD-L1 expression (n=39). As measured by MSD’s proprietary immunohistochemistry (IHC) clinical trial assay, tumours were classified as PD-L1 positive based on greater than or equal to one percent of tumour cells demonstrating expression of the PD-L1 marker, or any positive staining with the same reagent in tumour stroma. Enrollment was designed to include an equal number of Asian and non-Asian patients. The majority of patients had received two or more prior lines of therapy. (1)
In the study, tumour shrinkage was demonstrated in 40.5 percent (15/37) of evaulable patients who had measurable disease with one post baseline scan, per RECIST v1.1 criteria.
Adverse events were consistent with previously reported safety data for pembrolizumab. The most common investigator-assessed, treatment-related adverse events (occurring in greater than five percent) included hypothyroidism (12.8%) and fatigue (12.8%). Grade 3-5 investigator-assessed, treatment-related adverse events occurred in a total of three patients, with one patient each in peripheral sensory neuropathy (Grade 3), hypoxia (Grade 5) and pneumonitis (Grade 4). No infusion-related reactions were observed and no patients discontinued pembrolizumab due to a treatment-related adverse reaction. One treatment-related death due to hypoxia, as assessed by the investigator, was reported. (1)
References:
- A Phase 1b Study of Pembrolizumab (Pembro; MK-3475) in Patients With Advanced Gastric Cancer. Muro K, Bang JY, Shankaran V et al. Presented at ESMO, 26-30 September 2014, Madrid, Spain.
- Stomach cancer risks and causes. Cancer Research UK. Accessed from http://www.cancerresearchuk.org/about-cancer/type/stomach-cancer/about/stomach-cancer- risks-and-causes September 2014.
