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Poster display session

1352 - Phase 2 study of pembrolizumab alone or combined with acalabrutinib in platinum-refractory metastatic urothelial carcinoma (mUC)


10 Sep 2017


Poster display session


Immunotherapy;  Urothelial Cancers


Tian Zhang


Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371


T. Zhang1, M. Harrison1, P. O'Donnell2, A. Alva3, N. Hahn4, L.J. Appleman5, J. Cetnar6, J. Burke7, M. Fleming8, M. Milowsky9, A. Mortazavi10, N. Shore11, E.V. Schmidt12, C. Kresja13, T. Chen13, B. Bitman13, R. Izumi13, A. Hamdy13, D.J. George1

Author affiliations

  • 1 Duke Cancer Institute, Duke University Medical Center, 27710 - Durham/US
  • 2 Department Of Medicine, University of Chicago Medical Center, Chicago/US
  • 3 Urology Oncology, University of Michigan Medical Center, Ann Arbor/US
  • 4 Department Of Oncology And Urology, Johns Hopkins University, Baltimore/US
  • 5 Department Of Medicine, University of Pittsburgh Cancer Institute, 15232 - Pittsburgh/US
  • 6 Ohsu Healthcare, Oregon Health and Science University Center for Health, Portland/US
  • 7 Medical Oncology, Rocky Mountain Cancer Centers, Aurora/US
  • 8 Medical Oncology, Virginia Oncology Associates, Norfolk/US
  • 9 Department Of Medicine, Division Of Hematology And Oncology, Lineberger Comprehensive Cancer Center, Chapel Hill/US
  • 10 Internal Medicine, James Cancer Hospital, The Ohio State University, Columbus/US
  • 11 Atlantic Urology Clinics, Carolina Urologic Research Center, 29572 - Myrtle Beach/US
  • 12 N/a, Merck & Co., Inc., Kenilworth/US
  • 13 N/a, Acerta Pharma, Redwood City/US


Abstract 1352


PD-1/PD-L1 inhibitors have shown clinical benefit in mUC; however, the ORR is 15-25%, highlighting the need for more effective therapies. Gunderson, et al 2015 showed activation of Bruton tyrosine kinase (BTK) in myeloid cells of the pancreatic tumor microenvironment. As myeloid suppression impairs T-cell anti-tumor function, BTK inhibition may augment checkpoint inhibitor T-cell activation. This study assessed safety and efficacy of the PD-1 inhibitor pembrolizumab (P) alone or with the BTK inhibitor acalabrutinib (PA) in mUC.


Patients (pts) with mUC who progressed with ≥1 line of platinum chemotherapy were randomized 1:1 to P (200 mg Q3W IV) or PA (200 mg Q3W+100 mg BID PO). Pts who progressed (irRECIST) with monotherapy were permitted to cross over to combination therapy. Primary objectives were safety and ORR (local review, RECIST 1.1). Secondary endpoints included PFS and OS. Tumor PD-L1 expression was evaluated by Q2Solutions.


Between Jun 2015 and Jan 2016, 75 pts were treated with P (n = 35) or PA (n = 40); cross over, n = 10. Median age, 66 y; men, 76%; ECOG PS 0-1, 97%; median prior therapies, 2 (range, 1-4). In P/PA median (mos) time on study treatment, 2.96/1.94; median follow-up, 11.2/6.1. Grade 3-4 treatment-emergent AEs (%) in ≥ 15% of P or PA was anemia (20) in P and fatigue (23), increased alanine aminotransferase (23), urinary tract infection (18), and anemia (15) in PA. There were 3 fatal AEs in PA: hemoptysis and sepsis (unrelated); pneumonia (P-related). ORR was 26% (CR, 9%) with P and 20% (CR, 10%) with PA. Median PFS was similar between treatment arms; median OS was 11.4 and 6.3 mos in P vs PA (Table). Most pts (49/60) had PD-L1+ tumors; expression was not associated with improved ORR (Table).Table:


Pembrolizumab n = 35Pembrolizumab + acalabrutinib n = 40
Safety, n (%) (excluding events after cross over)
Any grade 3-4 AE17 (49)29 (73)
Any treatment-related grade 3-4 AE6 (17)21 (53)
Any grade 3-4 SAE12 (34)20 (50)
Any treatment-related 3-4 SAE0 (0)6 (15)
AE leading to study drug discontinuation7 (20)15 (38)
Grade 5 AE0 (0)3 (8)
Treatment-emergent AEs, n (%) (any grade, ≥30% of all pts)
Fatigue16 (46)33 (83)
Decreased appetite13 (37)17 (43)
Diarrhea7 (20)15 (38)
Anemia7 (20)14 (35)
Vomiting10 (29)12 (30)
ORR, % (95% CI) [n/N]
Overall population26 (13, 43) [9/35]20 (9, 36) [8/40]
PD-L1+ population23 (8, 45) [5/22]22 (9, 42) [6/27]
Median PFS, mo (95% CI)1.6 (1.4, 4.2)2.2 (1.4, 3.5)
Median OS, mo (95% CI)11.4 (5.7, NE)6.3 (3.6, 12.3)
12 mo OS, % (95% CI)44.1 (27.2, 59.8)38.5 (23.5, 53.3)

AE, adverse event; CI, confidence interval; mo, month; NE, not estimable; ORR, overall response rate; PFS, progression-free survival; SAE, serious adverse event; OS, overall survival.


Most pts tolerated the study treatment, although more PA-treated pts had grade 3-4 AEs. Acalabrutinib plus pembrolizumab did not improve ORR over pembrolizumab alone in pts with mUC, regardless of PD-L1 status.

Clinical trial identification


Legal entity responsible for the study

Acerta Pharma


Acerta Pharma


T. Zhang: Stock ownership: Capio Biosciences; Consulting/Advisory Role: Bayer, GI Therapeutics; Research Funding: Janssen, Acerta Pharma, Pfizer, Merrimack, StemCentrX. M. Harrison: Research Funding: Acerta, Bristol-Myers Squib, Genentech, Merck, Pfizer; Consulting/Advisory Role: AstraZeneca, Exelixis, Genentech; Speaker\'s Bureau: AstraZeneca, Exelixis, Genentech. P. O\'Donnell: Stock: DVA, PrescriptIQ, AGN; Honoraria: Algeta ASA, Genentech/ROG, NVS, American Medical Forum, MRK, AstraZeneca, Astellas, Seattle Genetics, INO, Janssen, PRXL; Rsrch Fund: BI, MRK, Genentech/ROG, AZN/Medimmune, Acerta, Janssen; Exprt Testmny: Trinity Health. A. Alva: Speakers Bureau: AstraZeneca; Research Funding: Bayer, Merck, Genentech, and Progenics. N. Hahn: Advisory: OncoGeneX, AstraZeneca, Merck, Bristol-Myers Squib, Genentech, Inovio, Principia Biopharma, Champions Oncology, Health Advances, TARIS Biomedical, Seattle Genetics; Research Funding: Novartis, OncoGeneX, Mirati, Merck, Genentech, Bristol-Myers Squib, Heat Biologics, Acerta, AstraZeneca, Principia Biopharma. L.J. Appleman: Research Funding: Acerta Pharma. J. Burke: Consulting or Advisory Role: Pfizer, Incyte, Celgene, Genentech, Bayer; Travel Expenses: TG Therapeutics. M. Fleming: Speaker\'s bureau: Genentech. M. Milowsky: Advisory: Inovio Pharmaceuticals, Genentech, AstraZeneca; Research Funding: Mirati, Pfizer, Cerulean, Merck, Seattle Genetics, Acerta, BioClin, Roche/Genentech, Bristol-Myers Squibb, X4 Pharma, MedImmune, Incyte, Innocrin Pharma, Inovio Pharma. A. Mortazavi: Research Funding: Acerta Pharma, Genentech, Merck, Novartis; Honoraria: Motive Medical Intelligence; Consultancy/Advisory Role: Genentech-Roche. N. Shore: Consulting or Advisory Role: Amgen, Astellas, Bayer, Dendreon, Ferring Pharmaceuticals, Janssen, Medivation, Sanofi, Tolmar, Inc; Speaker\'s Bureau: Janssen, Bayer, Dendreon. E.V. Schmidt: Employment: MSD, Merck; Stock: MSD. C. Kresja, T. Chen, A. Hamdy: Employment: Acerta Pharma. B. Bitman: Employment: Acerta Pharma; Stock: AstraZeneca. R. Izumi: Employment/Equity Ownership/Patents: Acerta Pharma. D.J. George: Rsrch Suprt and Cnsltnt: Astellas/Mediviation, Byr, Bristol-Myers Squib, Exelixis, J&J, Novartis, Pfizer, Viamet/Innocrin Rshrch Suprt: Acerta, Gntech, Millennium Cnsltnt: Acceleron, Clovis, Dendreon/Valeant, Merck, Myovant Spker: Byr, Dendreon/Valeant, Snofi-Avnts. All other authors have declared no conflicts of interest.

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