title: (90)Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies.
abstract: BACKGROUND
  For patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering (90)Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine.
  
  
  METHODS
  Fifty-eight patients with three (2-7) median prior treatments were treated on Arm A (N=29, (90)Y-clivatuzumab tetraxetan, weekly 6.5 mCi/m(2)doses×3, plus gemcitabine, weekly 200 mg/m(2) doses×4 starting 1 week earlier) or Arm B (N=29, (90)Y-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m(2)doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated.
  
  
  RESULTS
  Cytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3-9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan-Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29-0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4 months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1 year.
  
  
  CONCLUSIONS
  Clinical studies of (90)Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting.
authors.affiliation: Virginia Mason Medical Center, Seattle, WA, United States.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Picozzi
authors.affiliation: Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, AZ, United States.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, United States.
authors.forename: Maeve A
authors.initials: MA
authors.lastname: Lowery
authors.affiliation: Weill Cornell Medical College, New York, NY, United States.
authors.forename: Allyson J
authors.initials: AJ
authors.lastname: Ocean
authors.affiliation: Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA, United States.
authors.forename: Edith P
authors.initials: EP
authors.lastname: Mitchel
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, United States.
authors.forename: Bert H
authors.initials: BH
authors.lastname: O'Neil
authors.affiliation: Helen F. Graham Cancer Center at Christiana Care Health System, Newark, DE, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Guarino
authors.affiliation: US Oncology Phase II Group, Virginia Oncology Associates, Norfolk, VA, United States.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Conkling
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, United States.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Cohen
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
authors.forename: Nathan
authors.initials: N
authors.lastname: Bahary
authors.affiliation: Whittingham Cancer Center at Norwalk Hospital, Norwalk, CT, United States.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Frank
authors.affiliation: Banner MD Anderson Cancer Center, Gilbert, AZ, United States.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Dragovich
authors.affiliation: St Luke's Mountain States Tumor Institute, Meridian, ID, United States.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Bridges
authors.affiliation: Comprehensive Cancer Centers of Nevada, Las Vegas, NV, United States.
authors.forename: Fadi S
authors.initials: FS
authors.lastname: Braiteh
authors.affiliation: Indiana University Health Center for Cancer Care, Goshen, IN, United States.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Starodub
authors.affiliation: University of New Mexico Health Science Center, Albuquerque, NM, United States.
authors.forename: Fa-Chyi
authors.initials: FC
authors.lastname: Lee
authors.affiliation: Lacks Cancer Center, Saint Mary's Health Care, Grand Rapids, MI, United States.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Gribbin
authors.affiliation: Tyler Cancer Center, US Oncology Research, Tyler, TX, United States.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Richards
authors.affiliation: Virginia Mason Medical Center, Seattle, WA, United States.
authors.forename: Marie
authors.initials: M
authors.lastname: Lee
authors.affiliation: Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, AZ, United States.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Korn
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, United States.
authors.forename: Neeta
authors.initials: N
authors.lastname: Pandit-Taskar
authors.affiliation: Weill Cornell Medical College, New York, NY, United States.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Goldsmith
authors.affiliation: Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA, United States.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Intenzo
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, United States.
authors.forename: Arif
authors.initials: A
authors.lastname: Sheikh
authors.affiliation: Helen F. Graham Cancer Center at Christiana Care Health System, Newark, DE, United States.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Manzone
authors.affiliation: Immunomedics, Inc., Morris Plains, NJ, United States.
authors.forename: Heather
authors.initials: H
authors.lastname: Horne
authors.affiliation: Immunomedics, Inc., Morris Plains, NJ, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sharkey
authors.affiliation: Immunomedics, Inc., Morris Plains, NJ, United States.
authors.forename: William A
authors.initials: WA
authors.lastname: Wegener
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, United States.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: O'Reilly
authors.affiliation: Immunomedics, Inc., Morris Plains, NJ, United States; Center for Molecular Medicine and Immunology/Garden State Cancer Center, Morris Plains, NJ, United States. Electronic address: dmg.gscancer@att.net.
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.affiliation: Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, AZ, United States.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D009077:Mucins; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D003841:Deoxycytidine; C000589320:clivatuzumab; D000093542:Gemcitabine
keywords: Antibody; Clivatuzumab tetraxetan; Gemcitabine; Pancreatic cancer; Radioimmunotherapy; Yttrium-90