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 urothelial cancer (also known as bladder cancer). The early findings presented showed a confirmed overall response rate of 24% with pembrolizumab as monotherapy, as measured by RECIST v1.1, central review (n= 7/29: 95% CI, 10.3-43.5) including a complete response rate of 10% (3/29).
At the time of analysis, response durations ranged from 16 to 40+ weeks with six of the seven responders continuing on therapy. In the ongoing study, 64% (61/95) of patients screened had tumours that were determined to be positive for PD-L1 expression. (1)
These data, from a cohort of the ongoing Phase 1b KEYNOTE-012 study, were presented, as part of a late-breaking oral session, by Dr Elizabeth R. Plimack, Fox Chase Cancer Center, Philadelphia, at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain (ABSTRACT #LBA23).
“Although at this stage the dataset is small, we are encouraged by the response rate, complete response rate, and the durability of the response in patients suffering from advanced bladder cancer,” said Dr. Alise Reicin, vice president, oncology, Merck Research Laboratories. “As communicated previously, based on these data, MSD will initiate a Phase 3 study this year to better understand the potential of pembrolizumab in advanced bladder cancer.”
Early findings for investigational use of pembrolizumab in advanced bladder 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 bladder cancer whose tumours were determined to be positive for PD-L1 expression (n=29). As measured by Merck’s proprietary immunohistochemistry (IHC) clinical trial assay, tumours were classified as PD-L1 positive based on greater than or equal to 1% of tumour cells demonstrating expression of the PD-L1 marker, or any positive staining with the same reagent in tumour stroma. The majority of patients had received one or more prior lines of therapy. (1)
At six months, 58% of patients were alive and median overall survival was 9.3 months (95% CI, 3.6-NR). Additionally, tumour shrinkage was achieved in 64% of evaluable patients with one post-baseline treatment scan. Analysis of the relationship between PD-L1 expression and clinical outcomes is ongoing. (1)
Adverse events were consistent with previously reported safety data for pembrolizumab. The most common investigator-assessed, treatment-related adverse events (occurring in greater than or equal to two patients) included fatigue (18%), peripheral oedema (12%), and nausea (9%). Grade 3-5 investigator-assessed, treatment-related adverse events occurred in a total of four patients. One infusion-related reaction was observed and one patient discontinued pembrolizumab due to a treatment-related adverse reaction. There were no treatment-related deaths. (1)
References
1 A Phase 1b Study of Pembrolizumab (Pembro; MK-3475) in Patients With Advanced Urothelial Cancer. Plimack ER, Gupta S, Bellmunt J et al. Presented at ESMO, 26-30 September 2014, Madrid, Spain.
2 Bladder cancer risks and causes. Cancer Research UK. Accessed from http://www.cancerresearchuk.org/about-cancer/type/bladder-cancer/about/bladder-cancer- risks-and-causes in September 2014.
