Activation of the PD-1 pathway has been implicated in resistance to BCG therapy. Pembrolizumab (pembro), a checkpoint inhibitor with significant activity in patients (pts) with metastatic urothelial carcinoma, was evaluated in this population. KEYNOTE-057 (NCT02625961) is a single-arm phase 2 study of the efficacy and safety of pembro in pts with HR, BCG-unresponsive NMIBC. Preliminary results for cohort A (carcinoma in situ [CIS] or CIS plus papillary tumor) are presented.
Eligible pts had histologically confirmed high-grade BCG-unresponsive NMIBC, including CIS alone or combination of CIS and papillary disease (cohort A), had been treated with adequate BCG therapy (at least 5/6 induction instillations and 2/3 maintenance therapy instillations), and were unable or unwilling to undergo radical cystectomy. Pts received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. The primary end point for cohort A was complete response (CR); key secondary end points were safety and duration of response. Pts found to have HR NMIBC or progressive disease during treatment were required to discontinue.
At the time of data cutoff, 101 pts were enrolled in cohort A. Median follow-up was 9.4 mo (range 0.2-21.2). At mo 3, CR rate by central assessment was 36.5% (95% CI 26.3-47.6) in 85 evaluable pts. Among the 31 pts with CR at mo 3, median duration of CR was 8.1 mo (range 0+ to 13.7+). Estimated proportion of pts with response duration ≥6 mo was 85.6%. Treatment-related adverse events (AEs) occurred in 54 pts (55.7%); most common (≥5%) were diarrhea (9.3%), pruritus (9.3%), fatigue (7.2%), hypothyroidism (5.2%), maculopapular rash (5.2%), and arthralgia (5.2%). Treatment-related grade 3-5 AEs occurred in 11 pts (11.3%); 1 death was considered treatment related. Immune-mediated AEs occurred in 15 pts (15.5%) and were grade 3/4 in 2 pts (2.1%).
Pembro exhibits encouraging antitumor activity in pts with HR and BCG-unresponsive NMIBC with CIS. The safety profile of pembro in this pt population is consistent with that of previous studies. KEYNOTE-057 is ongoing.
Clinical trial identification
Legal entity responsible for the study
Merck & Co., Inc.
Merck & Co., Inc.
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co., Inc., Kenilworth, NJ, USA.
R. de Wit: Consultancy: Sanofi, Merck, Roche; Speaker fees: Sanofi, Merck. G.S. Kulkarni: Advisory board member: Ferring, Janssen, Astellas, Amgen, Bayer, Theralase. Research funding: Biosyent. Honoraria: Abbvie, TerSera. Travel expenses, including accommodations: Abbvie, Sanofi, TerSera, Bayer. E.A. Singer: Research funding: Astellas/Medivation. L. Krieger: Advisory board member: Bayer, AstraZeneca, BMS, MSD, Roche, Janssen, Ipsen, Novartis, Pfizer, Astellas Speakers' bureau: MSD, Bayer, BMS, Ipsen Honoraria: Bayer, Ipsen, BMS, Novartis, Janssen, Astellas, MSD Travel expenses: Astella, Ipsen, Roche, MSD. P. Grivas: Honoraria: Merck & Co.; Genentech; Bristol-Myers Squibb; AstraZeneca; EMD Serono; Clovis Oncology; Seattle Genetics; Foundation Medicine; Driver Inc. D. Bajorin: Advisory board member: Merck, Genentech, Bristol Myers Squibb, Urogen, Novartis; Research funding: Merck, Novartis. A. Kamat: Research funding: FKD, Merck, Telesta, Adolor. Honoraria TMC Innovation, Merck, BMS, Arquer, MDxHealth, Photocure, Theralase, Cepheid, Medac, Asieris, Pfizer, Astra Zeneca. E. Kapadia, K. Nam, T. Frenkl: Employee and stockholder: Merck & Co., Inc. A. Balar: Advisory board member: Genentech, Merck, Incyte, AstraZeneca, Seattle Genetics, Pfizer/EMD Serono. Research funding: Genentech, Merck, AstraZeneca. Honoraria: Merck, AstraZeneca, Genentech. All other authors have declared no conflicts of interest.