Pembrolizumab Monotherapy for Unresponsive NMIBC: Keynote-057 Cohort B Results

Patients with BCG-unresponsive HR NMIBC (per FDA) who are ineligible or refuse to receive RC were the focus of the single-arm, multicohort phase 2 KEYNOTE-057 trial (NCT02625961), which aims to explore the safety and efficacy of pembro monotherapy. The clinical complete response rate at 3 months was 41% in cohort A (carcinoma in situ [CIS] papillary tumors), leading to the approval of pembro monotherapy for such pts in the United States. Herein, they report on the findings from Cohort B. (papillary tumors without CIS).

Patients had high-risk non-small-cell lung cancer (HR NMIBC) with papillary tumors alone (high-grade Ta or any-grade T1) and an ECOG performance status (PS) of 0-2 and were 18 years old. Patients (Pts) were given pembro 200 mg every three weeks (Q3W) for approximately 35 cycles (2 years). Cancer was evaluated at 12 weeks and every 12 weeks after that for progression or recurrence; CT urography was performed every 24 weeks. Cohort B’s primary end points were safety and the 12-month disease-free survival (DFS) rate of HR NMIBC based on central pathology/radiology evaluation. This was based on the assumption that the 12-month DFS rate of HR NMIBC would be greater than 20%. 12-month disease-free survival (DFS) rate, progression-free survival (PFS) to worsening of grade, stage, or death, progression-free survival (PFS) to muscle invasion, metastasis, or death, and overall survival were secondary efficacy end goals (OS).

During the course of 132 cycles, the median number of pembro treatments given to each patient was 9.5. (range, 1.0-35.0). Patients had a median age of 72 years (range, 37-87); 43.2% were at T1 stage; all patients (100%) had urothelial histology; 78.8% were male; and patients had received a median of 10 prior BCG instillations (range, 6-33). After a median of 45,4 months (range, 14.9-77.1). After discontinuing pembro, 31 points (or 23.5% of the total) developed RC. Around 97 patients (73.5%) experienced adverse events (AEs) linked to their therapy, with 19 (14.4%) experiencing a treatment-related AE of grade 3/4 and 14 (10.6%) discontinuing treatment as a result of an AE. Acute adverse events (AEs) unrelated to therapy did not result in any fatalities.

At 45 mo of follow-up, Pembro demonstrated significant antitumor activity in patients with BCG-unresponsive non-CIS papillary HR NMIBC. No new safety signals emerged, and the toxicity was moderate and comparable to that seen in cohort A. Patients with non-CIS papillary HR NMIBC who did not respond to BCG and were either unwilling or unable to undergo RC may also benefit from pembro monotherapy, according to the study’s findings.

Source: https://meetings.asco.org/abstracts-presentations/216468

Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02625961/

Andrea Necchi, Mathieu Roumiguié, Ahmet Adil Esen, Thierry Lebret, Ronald De Wit, Neal D. Shore, Dean F. Bajorin, Laurence E. M. Krieger, Shuya Kandori, Edward M. Uchio, Ho Kyung Seo, Joost Boormans, Ashish M. Kamat, Eric A. Singer, Petros Grivas, Hiroyuki Nishiyama, Kijoeng Nam, Ekta Kapadia, Margot Van den Sigtenhorst-Fijlstra, Girish S. Kulkarni; J Clin Oncol 41, 2023 (suppl 6; abstr LBA442), DOI: 10.1200/JCO.2023.41.6_suppl.LBA442