Abstract 2829
Background
Efficacy and safety of pembro in pts with HR BCG-unresponsive NMIBC was evaluated in the single-arm phase 2 KEYNOTE-057 study (NCT02625961); updated follow-up of interim data and exploratory HRQoL analyses are reported.
Methods
Pts with histologically confirmed HR BCG-unresponsive CIS with or without papillary tumors who received adequate BCG therapy and who were ineligible or refused radical cystectomy (cohort A) were eligible. Pts received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity; those who developed HR NMIBC or progressive disease were required to discontinue. Key end points: complete response rate (CRR), duration of response, and safety. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Bladder Cancer (FACT-Bl) scale.
Results
102 pts enrolled in cohort A as of enrollment cutoff. Median (range) duration of follow-up was 21.1 mo (4.6-33.4); CRR was 41.2% (95% CI, 31.5-51.4) by central assessment. Among 42 pts with CR, median CR duration was 13.5 mo (range, 0+ to 26.8+); 57.4% had CR ≥ 12 mo (Kaplan-Meier). 22 pts (52.4%) maintained CR at last follow-up. 20 (47.6%) experienced recurrent NMIBC after CR. At time of analysis, there were no occurrences of progression to muscle-invasive disease (T2) or metastatic bladder cancer. For pts with CR, HRQoL was stable over time. At a prespecified analysis timepoint of week 39, the majority of pts (71.1% for FACT-G total and 77.8% for FACT-G physical well-being score) had improved (≥7 or ≥ 3 point increase, respectively) or stable (change between –7 and +7 or –3 and +3 points, respectively) scores from baseline. Treatment-related adverse events (TRAEs) occurred in 67 (65.7%) pts; most frequent (≥10%) were fatigue (10.8%), pruritus (10.8%), and diarrhea (10.8%). Grade 3/4 TRAEs occurred in 13 (12.7%) pts.
Conclusions
Pembro continued to show encouraging antitumor activity in pts with HR BCG-unresponsive CIS with or without papillary tumors plus maintenance of HRQoL. The safety profile was consistent with the known profile of pembro.
Clinical trial identification
NCT02625961; December 9, 2015.
Editorial acknowledgement
Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
R. de Wit: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): Janssen; Advisory / Consultancy: Clovis. G.S. Kulkarni: Advisory / Consultancy: Ferring; Advisory / Consultancy: Janssen; Advisory / Consultancy: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Theralase; Research grant / Funding (self): Biosyent; Honoraria (self), Travel / Accommodation / Expenses: AbbVie; Honoraria (self), Travel / Accommodation / Expenses: TerSera; Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy: Amgen. J.L. Boormans: Advisory / Consultancy: BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Janssen; Research grant / Funding (self): GenomeDx Biosciences. L.E.M. Krieger: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy: Novartis; Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas. E.A. Singer: Research grant / Funding (self): Astellas/Medivation. D.F. Bajorin: Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy: Genentech; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Urogen; Advisory / Consultancy, Research grant / Funding (self): Novartis. A.M. Kamat: Research grant / Funding (institution): FKD; Honoraria (self), Research grant / Funding (institution): Merck; Research grant / Funding (institution): Telesta; Research grant / Funding (institution): Adolor; Honoraria (self): TMC Innovation; Honoraria (self): BMS; Honoraria (self): Arquer; Honoraria (self): MDxHealth; Honoraria (self): Photocure; Honoraria (self): Theralase; Honoraria (self): Cepheid; Honoraria (self): Medac; Honoraria (self): Asieris; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca. P. Grivas: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck & Co., Inc.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Educational unbranded activity: Genentech; Honoraria (self), Advisory / Consultancy: Dendreon; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Educational unbranded activity: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Exelixis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: Biocept; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Clovis Oncology; Honoraria (self), Advisory / Consultancy: EMD Serono; Honoraria (self), Advisory / Consultancy: Seattle Genetics; Honoraria (self), Advisory / Consultancy: Foundation Medicine; Honoraria (self), Advisory / Consultancy: Driver Inc.; Honoraria (self), Advisory / Consultancy: QED Therapeutics; Honoraria (self), Advisory / Consultancy: Heron Therapeutics; Honoraria (self), Advisory / Consultancy: Janssen; Research grant / Funding (institution): Mirati; Research grant / Funding (institution): Oncogenex; Research grant / Funding (institution): Bavarian Nordic, Immunomedics. B.R. Konety: Advisory / Consultancy, Research grant / Funding (institution): Photocure; Advisory / Consultancy: Pacific Edge; Advisory / Consultancy: Taris; Advisory / Consultancy: Boston Scientific; Advisory / Consultancy: NxThera; Research grant / Funding (institution): Genomic Health; Research grant / Funding (institution): Merck; Research grant / Funding (institution): BMS. T. Saretsky: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck and Co., Inc. H. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. K. Nam: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. E. Sbar: Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: MSD; Shareholder / Stockholder / Stock options: BMS; Shareholder / Stockholder / Stock options: Pfizer. A.V. Balar: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Pfizer/EMD Serono. All other authors have declared no conflicts of interest.
Resources from the same session
2743 - The Impact of Targeted Therapies and Immunotherapy in Melanoma Brain Metastases: a Systematic Review and Meta-Analysis
Presenter: Mario Mandala
Session: Poster Display session 3
Resources:
Abstract
5479 - Intracranial Anti-Tumor Activity in Melanoma Brain Metastases with Encorafenib Plus Binimetinib: A Multicenter, Retrospective Analysis
Presenter: Jose Lutzky
Session: Poster Display session 3
Resources:
Abstract
3560 - Outcomes of Patients with Melanoma Brain Metastases (MBM) Treated with Standard of Care Therapy After Being Excluded from MBM-Specific Clinical Trials
Presenter: Kourtney Holbrook
Session: Poster Display session 3
Resources:
Abstract
3175 - The analysis of current treatment outcomes in melanoma patients with brain metastases
Presenter: Joanna Placzke
Session: Poster Display session 3
Resources:
Abstract
4550 - A multivariate model to define prognostic groups among patients with melanoma brain metastases: a 10-year retrospective cohort study
Presenter: Giacomo Pelizzari
Session: Poster Display session 3
Resources:
Abstract
4191 - The immune landscape of melanoma significantly influences survival in patients with highly mutated tumors.
Presenter: Robert Ferguson
Session: Poster Display session 3
Resources:
Abstract
1625 - Final Results from Phase II of Combination with Canerpaturev (formerly HF10), an Oncolytic Viral Immunotherapy, and Ipilimumab in Unresectable or Metastatic Melanoma in 2nd-or later line treatment
Presenter: Kenji Yokota
Session: Poster Display session 3
Resources:
Abstract
5346 - Evaluating polygenic risk score prediction model for melanoma prognosis
Presenter: Miriam Potrony
Session: Poster Display session 3
Resources:
Abstract
5477 - Impact of sarcopenia in patients with metastatic melanoma treated with immunotherapy
Presenter: Maria Grazia Vitale
Session: Poster Display session 3
Resources:
Abstract
3469 - Ancillary evaluation of systemic immune antitumor response (SIAR) and tumor growth rate (TGR) of patients (pts) with metastatic melanoma (MM) treated with radiotherapy (RT) combined with ipilimumab (ipi) in the phase 1 study Mel-Ipi-Rx.
Presenter: Celine Boutros
Session: Poster Display session 3
Resources:
Abstract