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
2115 - Preclinical in vivo screening to predict responder patients depend on EGFR status
Presenter: Yejin Kim
Session: Poster Display session 3
Resources:
Abstract
3349 - Interplay between miR-17-5p and MALAT-1 Shapes The Cytokine Storm in Triple Negative Breast Cancer (TNBC) Tumor Microenvironment
Presenter: Raghda Soliman
Session: Poster Display session 3
Resources:
Abstract
4014 - Clinical verification on the relationship between lipid metabolism and the immune microenvironment of breast cancer
Presenter: Wataru Goto
Session: Poster Display session 3
Resources:
Abstract
4158 - The clinical and transcriptional signatures of human CD204 reveal an applicable marker for tumor associated macrophage in breast cancer
Presenter: Yunjie He
Session: Poster Display session 3
Resources:
Abstract
5392 - Activated effector T cells co-expressing multiple inhibitory receptors (IRs) are enriched in the tumor immune microenvironment in high grade serous ovarian cancer (HGSOC)
Presenter: Alice Bergamini
Session: Poster Display session 3
Resources:
Abstract
2617 - Oncolytic reovirus as a new anti-tumor strategy in castration resistant prostate cancer
Presenter: Yunlim Kim
Session: Poster Display session 3
Resources:
Abstract
2995 - Dysregulation of helper T lymphocytes in esophageal squamous cell carcinoma (ESCC) patients is highly associated with aberrant production of miR-21
Presenter: Ali Memarian
Session: Poster Display session 3
Resources:
Abstract
3597 - Myeloid derived suppressor cells but not regulatory T cells are associated with adaptive immunity and clinical outcomes in anal squamous cell carcinoma
Presenter: Christophe Borg
Session: Poster Display session 3
Resources:
Abstract
3430 - Evaluation of immune responses among responders (R) and non-responders (non-R) in a humanized mouse model with colorectal cancer (CRC) xenografts treated with combination immunotherapy
Presenter: Juan Marín Jiménez
Session: Poster Display session 3
Resources:
Abstract
1995 - ¬¬Advanced melanoma patients with high CD16+ macrophages have better response and survival to anti-PD-1 based immunotherapy
Presenter: Hansol Lee
Session: Poster Display session 3
Resources:
Abstract