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Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma.
Lu, Tong; Gibiansky, Leonid; Li, Xiaobin; Li, Chunze; Shi, Rong; Agarwal, Priya; Hirata, Jamie; Miles, Dale; Chanu, Pascal; Girish, Sandhya; Jin, Jin Yan; Lu, Dan.
Affiliation
  • Lu T; Genentech, Inc, South San Francisco, CA, USA.
  • Gibiansky L; QuantPharm LLC, North Potomac, MD, USA.
  • Li X; Genentech, Inc, South San Francisco, CA, USA.
  • Li C; Genentech, Inc, South San Francisco, CA, USA.
  • Shi R; Genentech, Inc, South San Francisco, CA, USA.
  • Agarwal P; Genentech, Inc, South San Francisco, CA, USA.
  • Hirata J; Genentech, Inc, South San Francisco, CA, USA.
  • Miles D; Genentech, Inc, South San Francisco, CA, USA.
  • Chanu P; Genentech, Inc./F. Hoffmann-La Roche Ltd, Lyon, France.
  • Girish S; Genentech, Inc, South San Francisco, CA, USA.
  • Jin JY; Genentech, Inc, South San Francisco, CA, USA.
  • Lu D; Genentech, Inc, South San Francisco, CA, USA.
Leuk Lymphoma ; 61(12): 2905-2914, 2020 12.
Article in En | MEDLINE | ID: mdl-32705923
Exposure-response relationships were investigated to assess the risk/benefit of polatuzumab vedotin (pola) + bendamustine-rituximab (pola + BR) in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Analyses were conducted in pivotal study GO29365 (NCT02257567; BR/pola + BR/pola + BG [BG: bendamustine-obinutuzumab]; 1.8 mg/kg pola, every 3 weeks [Q3W], six cycles), and supportive studies DCS4968g (NCT01290549) and GO27834 (NCT01691898) (pola/pola + R/pola + G; 0.1-2.4 mg/kg pola Q3W; eight-cycle landmark), separately. Exposure was characterized as simulated cycle-6 AUC and Cmax for antibody-conjugated mono-methyl auristatin E (acMMAE) and unconjugated MMAE. Supportive studies showed response rate and safety risk (grade ≥2 peripheral neuropathy; grade ≥3 anemia) increased with exposure, suggesting not to dose below 1.8 mg/kg (up to eight-cycle) for balancing safety and efficacy. Pivotal study with limited exposure range showed no exposure-safety relationship and slightly positive exposure (acMMAE)-efficacy relationship for overall survival. The exposure-response analyses and the observed risk/benefit characteristics in pivotal study supported pola (1.8 mg/kg) +BR Q3W for six cycles in R/R DLBCL patients.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lymphoma, Non-Hodgkin / Lymphoma, Large B-Cell, Diffuse / Immunoconjugates Limits: Humans Language: En Journal: Leuk Lymphoma Journal subject: HEMATOLOGIA / NEOPLASIAS Year: 2020 Document type: Article Affiliation country: United States Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lymphoma, Non-Hodgkin / Lymphoma, Large B-Cell, Diffuse / Immunoconjugates Limits: Humans Language: En Journal: Leuk Lymphoma Journal subject: HEMATOLOGIA / NEOPLASIAS Year: 2020 Document type: Article Affiliation country: United States Country of publication: United States