Safety and pharmacokinetics of polatuzumab vedotin in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma: a phase 1 dose-escalation study. (8th October 2020)

• Record Type: Journal Article
• 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
• Is Part Of: Japanese journal of clinical oncology. Volume 51:Number 1(2021)
• Page Start: 70
• Page End: 77
• Publication Date: 2020-10-08
• Subjects: polatuzumab vedotin -- phase 1 clinical trial -- pharmacokinetics -- B-cell lymphoma; Oncology -- Periodicals; Cancer -- Periodicals; 616.994005
• DOI: 10.1093/jjco/hyaa169
• Languages: English
• ISSNs: 0368-2811

Abstract

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. Abstract : 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.