Keytruda Elicits Complete Response in 40% of Group of High-risk Bladder Cancer Patients, Early Phase 2 Trial Data Show

Keytruda Elicits Complete Response in 40% of Group of High-risk Bladder Cancer Patients, Early Phase 2 Trial Data Show

The immune checkpoint inhibitor Keytruda (pembrolizumab) completely eliminated tumors in almost 40% of a group of bladder cancer patients in an ongoing Phase 2 trial, Merck (known as MSD outside the U.S. and Canada) announced. The interim analysis also found an additional 55% of these high-risk patients showed a reduction in tumor burden.

The open-label trial, called KEYNOTE-057 (NCT02625961), is enrolling patients with high risk non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) — where the disease is still confined to the bladder wall — and with or without papillary disease (cancer cells are arranged in finger-like projections). All failed standard treatment and could not or chose not to undergo bladder surgery.

The findings were recently presented during the European Society of Medical Oncology (ESMO) 2018 Annual Meeting, in Munich. The oral presentation was titled, “Pembrolizumab for High-Risk (HR) Non–Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guérin (BCG): Phase 2 KEYNOTE-057Trial.”

Keytruda is a type of therapy called an immune checkpoint inhibitor. It binds to the PD-1 protein on immune T-cells, blocking its binding to PD-L1 on tumor cells. Cancer cells use the interaction between PD-1 and PD-L1 to evade immune attack. Treatment with Keytruda is intended to increase the immune system’s anti-cancer response.

The medicine is approved for a kind of bladder and urinary tract cancer called urothelial carcinoma, and researchers are now investigating its efficacy among NMIBC patients.

KEYNOTE-057 includes patients who failed to respond to Bacillus Calmette-Guérin (BCG) therapy, the current standard of care for NMIBC. All enrolled are being treated with pembrolizumab, 200 mg, given intravenously every three weeks for up to 24 months.

Patients either have CIS, with or without papillary disease (cohort A), or papillary disease without CIS (cohort B). For cohort A, the study’s main objective is to determine the rates of complete responses, while disease-free survival will serve as primary goal for cohort B.

Interim data presented at the meeting was from cohort A, after a median follow-up of 14 months.

This group included 103 patients, and 40 (38.8%) had achieved a complete response at three months, with responses lasting six months or longer in 80% of these patients. At the time of the analysis, 25% of complete responders had seen their cancer return while others did not, and one patient without disease recurrence started an alternative treatment.

The three-month response rate, or responses to treatment other than complete, reached 55.3%, amounting to an overall response rate of 94.1%.

The safety profile of Keytruda was similar to that of other trials for the medicine. Nearly two-thirds of patients experienced treatment-related adverse events, with the most common being itchy skin, fatigue, diarrhea, and hypothyroidism, meaning the thyroid produces hormones at lower-than-normal levels.

Of these patients, 12.6% experienced a serious to life-threatening adverse event, including one treatment-related death.

“The nearly 40 percent complete response rate with Keytruda in patients with high-risk non-muscle invasive bladder cancer is encouraging and adds to the growing body of data showing the anti-tumor activity of Keytruda as monotherapy across different types of cancer,” Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories, said in a press release.

“There are few options for the treatment of recurrent non-muscle invasive bladder cancer, and we look forward to continuing to study Keytruda for the treatment of these patients whose disease has reoccurred and who have limited therapeutic options,” he concluded.

KEYNOTE-057 is still enrolling eligible patients — up to 260 people — at sites across the U.S. and Europe, and in Australia, Brazil, and Canada; more information is available here.