22 October 2018 - - US-based biopharmaceutical company Merck (NYSE: MRK) has presented results from an interim analysis of KEYNOTE-057, a Phase 2 trial evaluating Keytruda, Merck's anti-PD-1 therapy, for previously treated patients with high-risk non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ or CIS plus papillary disease (Cohort A).

An interim analysis of the study's primary endpoint showed a complete response rate of 38.8% (95% CI, 29.4-48.9) (n=103) at three months with Keytruda in patients whose disease was unresponsive to Bacillus Calmette-Guérin therapy, the current standard of care for this disease, and who were ineligible for or who refused to undergo radical cystectomy.

These results, as well as other study findings, are being presented TODAY in an oral session at the ESMO 2018 Congress (Abstract #864O).

KEYNOTE-057 is a Phase 2, single-arm, multi-cohort study evaluating KEYTRUDA as monotherapy in patients with high-risk NMIBC that has not responded to treatment with BCG therapy and who are ineligible for or who have refused to undergo radical cystectomy.

The study's primary endpoints are CR rate (Cohort A only) and disease-free survival rate (Cohort B only). The secondary endpoints include safety and duration of response.

Data presented at ESMO are from an interim analysis of patients with CIS or CIS plus papillary disease (Cohort A) (n=103).

Findings showed a CR rate of 38.8% (95% CI, 29.4-48.9) (n=40/103) at three months. The non-CR rate was 55.3% (95% CI, 45.2-65.1) (n=57/103) at three months, and patients had either persistent disease (CIS +/- papillary tumor), NMIBC stage progression (CIS +/- high-grade Ta at baseline to T1 disease) or extravesical disease. At the time of analysis, 72.5 % of responding patients had an ongoing response (n=29/40) and 25 % experienced recurrent disease after CR (n=10/40).

One patient who did not develop recurrent disease discontinued study treatment and started alternative therapy. No patients in Cohort A developed muscle invasive or metastatic urothelial carcinoma.

Of the patients who achieved a CR at three months, 80 % had a CR lasting for six months or longer, based on the Kaplan-Meier method. The median duration of response was not yet reached (range, 0+ to 14.1+). The median follow-up was 14.0 months (range, 4.0-26.3 months).

The safety of Keytruda in KEYNOTE-057 was consistent with what has been seen in previous trials among patients treated with Keytruda monotherapy. Treatment-related adverse events (TRAEs) occurred in 63.1 % of patients.

The most common TRAEs with an incidence of 5 % or more were pruritus (10.7%), fatigue, diarrhea, hypothyroidism and maculopapular rash. Grade 3-5 TRAEs occurred in 13 patients (12.6%), and there was one treatment-related death, per investigator assessment.

The target enrollment for KEYNOTE-057 (ClinicalTrials.gov, NCT02625961) is 260 patients across two cohorts: patients with CIS or CIS plus papillary disease (Cohort A) (n=130) and patients with papillary disease without CIS (Cohort B) (n=130).

Patients in both cohorts receive Keytruda (200 mg fixed dose intravenously every three weeks) until recurrence, disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

In this study, BCG-unresponsive high-risk NMIBC is defined as persistent or recurrent disease despite adequate BCG therapy or stage progression despite adequate BCG induction therapy. Patients were considered high risk if their tumors were classified as T1, high-grade Ta and/or CIS based on the American Joint Committee on Cancer TNM system.

Bladder cancer begins when cells in the urinary bladder start to grow uncontrollably. As more cancer cells develop, they can form a tumor and spread to other areas of the body. Bladder cancers are described based on how far they have invaded into the wall of the bladder.

Non-muscle invasive bladder cancer occurs when the cancer has not grown into the main muscle layer of the bladder.

Eighty percent of bladder cancer patients are diagnosed with NMIBC. Worldwide, bladder cancer is the tenth most common cancer and the thirteenth most common cause of cancer death. It is estimated that almost 550,000 new cases of bladder cancer will be diagnosed in 2018.

Keytruda is an anti-PD-1 therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry's largest immuno-oncology clinical research programme. There are currently more than 850 trials studying Keytruda across a wide variety of cancers and treatment settings.

The Keytruda clinical programme seeks to understand the role of Keytruda across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers.