Safety and pharmacokinetics of polatuzumab vedotin in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma: a phase 1 dose-escalation study

• Published in: Japanese journal of clinical oncology 2021-01, Vol.51 (1), p.70-77
• Main Authors: Kinoshita, Tomohiro, Hatake, Kiyohiko, Yamamoto, Kazuhito, Higuchi, Yusuke, Murakami, Satsuki, Terui, Yasuhito, Yokoyama, Masahiro, Maruyama, Dai, Makita, Shinichi, Hida, Yukari, Saito, Tomohisa, Tobinai, Kensei
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Female; Humans; Immunoconjugates - adverse effects; Immunoconjugates - pharmacokinetics; Immunoconjugates - therapeutic use; Lymphoma, Follicular - drug therapy; Lymphoma, Large B-Cell, Diffuse - drug therapy; Male; Middle Aged; Original; Recurrence
• ISSN: 1465-3621; 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyaa169

Abstract Objective A phase 1 dose-escalation study of polatuzumab vedotin (pola) was conducted to assess safety, pharmacokinetics and preliminary antitumor activity of pola in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Methods Patients received pola (1.0 or 1.8 mg/kg) intravenously every 21 days until disease progression or intolerance. Intra-patient dose escalation was prohibited. Tolerability was determined by the standard 3 + 3 rule. Blood sampling was performed to characterize pharmacokinetics. Antitumor activity was evaluated through computed tomography and bone marrow sampling. Results Four patients received pola 1.0 mg/kg; three received 1.8 mg/kg. Patients had follicular lymphoma (n = 4) or diffuse large B-cell lymphoma (n = 3), median age of 62 years, received a median of 3 prior therapies; six were female. Pola was well tolerated in both cohorts, with no dose-limiting toxicities observed. The most common adverse event was peripheral sensory neuropathy (n = 4). Grade 3 adverse events were cholecystitis and neutrophil count decreased (one each; both 1.0 mg/kg), and syncope and cataract (one each; both 1.8 mg/kg). The plasma half-life of antibody-conjugate monomethyl auristatin E was 4.43–7.98 days, and systemic exposure of unconjugated monomethyl auristatin E was limited in both cohorts. Four patients achieved objective responses (three complete, one partial) without disease progression during the study. Conclusions This phase 1 dose-escalation study demonstrated that pola has an acceptable safety profile and offers encouraging antitumor activity to Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Pola 1.8 mg/kg, the recommended phase 2 dose, was tolerable in Japanese patients. This phase 1 dose-escalation study demonstrated that pola has an acceptable safety profile and offers encouraging antitumor activity to Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma.