Vincent J Picozzi1, Ramesh K Ramanathan2, Maeve A Lowery3, Allyson J Ocean4, Edith P Mitchel5, Bert H O'Neil6, Michael J Guarino7, Paul R Conkling8, Steven J Cohen9, Nathan Bahary10, Richard C Frank11, Tomislav Dragovich12, Benjamin B Bridges13, Fadi S Braiteh14, Alexander N Starodub15, Fa-Chyi Lee16, Thomas E Gribbin17, Donald A Richards18, Marie Lee1, Ronald L Korn2, Neeta Pandit-Taskar3, Stanley J Goldsmith4, Charles M Intenzo5, Arif Sheikh6, Timothy C Manzone7, Heather Horne19, Robert M Sharkey19, William A Wegener19, Eileen M O'Reilly3, David M Goldenberg20, Daniel D Von Hoff2. 1. Virginia Mason Medical Center, Seattle, WA, United States. 2. Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, AZ, United States. 3. Memorial Sloan-Kettering Cancer Center, New York, NY, United States. 4. Weill Cornell Medical College, New York, NY, United States. 5. Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA, United States. 6. UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, United States. 7. Helen F. Graham Cancer Center at Christiana Care Health System, Newark, DE, United States. 8. US Oncology Phase II Group, Virginia Oncology Associates, Norfolk, VA, United States. 9. Fox Chase Cancer Center, Philadelphia, PA, United States. 10. University of Pittsburgh Medical Center, Pittsburgh, PA, United States. 11. Whittingham Cancer Center at Norwalk Hospital, Norwalk, CT, United States. 12. Banner MD Anderson Cancer Center, Gilbert, AZ, United States. 13. St Luke's Mountain States Tumor Institute, Meridian, ID, United States. 14. Comprehensive Cancer Centers of Nevada, Las Vegas, NV, United States. 15. Indiana University Health Center for Cancer Care, Goshen, IN, United States. 16. University of New Mexico Health Science Center, Albuquerque, NM, United States. 17. Lacks Cancer Center, Saint Mary's Health Care, Grand Rapids, MI, United States. 18. Tyler Cancer Center, US Oncology Research, Tyler, TX, United States. 19. Immunomedics, Inc., Morris Plains, NJ, United States. 20. 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.
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.
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 cancerpatients beyond 2nd line and a Phase III trial of this combination is now underway in this setting.
Authors: David Akhavan; Paul Yazaki; Dave Yamauchi; Jennifer Simpson; Paul H Frankel; James Bading; David Colcher; Kofi Poku; Yi-Jen Chen; Dean Lim; Mihaela Cristea; Anna Wu; John Shively; Jeffrey Y C Wong Journal: Cancer Biother Radiopharm Date: 2020-01-07 Impact factor: 3.099
Authors: Ana P S Silva; Priscila V Coelho; Maristella Anazetti; Patricia U Simioni Journal: Hum Vaccin Immunother Date: 2016-11-10 Impact factor: 3.452
Authors: Kelly E Henry; Kyeara N Mack; Veronica L Nagle; Mike Cornejo; Adam O Michel; Ian L Fox; Maria Davydova; Thomas R Dilling; Nagavarakishore Pillarsetty; Jason S Lewis Journal: Mol Cancer Ther Date: 2021-08-04 Impact factor: 6.261