A phase I pharmacokinetic and safety study of polatuzumab vedotin in Japanese patients with relapsed/refractory b-cell non-Hodgkin lymphoma: A comparison with non-Japanese DCS4968g study.

Abstract

e19070 Background: Polatuzumab vedotin (PoV) is an antibody-drug conjugate (ADC) that contains a humanized anti-CD79b monoclonal antibody and a potent anti-mitotic agent, monomethyl auristatin E (MMAE). DCS4968g, a phase I study of PoV in patients (pts) with relapsed or refractory (r/r) B-cell NHL (Palanca-Wessels MC, et al. Lancet Oncol. 2015), showed that both monotherapy and combination with rituximab were effective with acceptable safety profiles in these pts. We conducted a phase I study (JO29138) to assess the safety, pharmacokinetics (PK), and efficacy of single agent PoV in Japanese pts, and compared results with those of DCS4968g. Methods: JO29138 was an open-label, multicenter 3+3 dose escalation study to assess the safety, tolerability, and PK of PoV in Japanese pts with r/r B-cell NHL. In JO29138, single agent PoV was administered intravenously at 1.0 or 1.8 mg/kg every 3 wks until disease progression. Results: As of 1 Oct 2015, 7 pts were enrolled (1.0 mg/kg cohort, 4 pts; 1.8 mg/kg cohort, 3 pts). Pt demographics were: 4 pts with FL and 3 pts with DLBCL; median age, 62 yrs; 6/7 female; median weight, 58 kg; median no. of prior therapies, 3. No dose-limiting toxicity was observed in either cohort. The only grade ≥ 3 AE was one grade 4 neutropenia in the 1.0 mg/kg cohort. The most common AE was peripheral sensory neuropathy, observed in 4 pts. Overall safety profile seems comparable with that of DCS4968g. PK profile of PoV showed long serum half-life, and the systemic exposure of unconjugated MMAE was limited. No distinct difference in PK profile between the 2 studies was observed. Preliminary response rate in JO29138 at 1.0 and 1.8 mg/kg was 43% (3/7) overall, comparable to the 43% (3/7) in DCS4968g. In JO29138, tumor lesions in 2 pts completely disappeared on CT. Four pts have received over 15 cycles of treatment without disease progression. Conclusions: The safety, PK, and efficacy of PoV monotherapy were reasonably comparable between Japanese and non-Japanese, and 1.8 mg/kg was tolerable as the recommended phase 2 dose. These results support further clinical studies of PoV, including combination with other antitumor agents. Clinical trial information: JapicCTI-142580.