Phase 1 Study of Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) Plus Rituximab In Japanese Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Inotuzumab ozogamicin (CMC-544) is a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. Inotuzumab ozogamicin targets CD22, which is expressed in the majority of B-cell non-Hodgkin lymphomas (NHL). The maximum tolerated dose of inotuzumab ozogamicin administered as a single agent was previously determined to be 1.8 mg/m² administered intravenously every 28 days, and clinical activity was shown in both non-Japanese and Japanese patients with relapsed or refractory B-cell NHL. Safety and efficacy data in non-Japanese patients with relapsed or refractory B-cell NHL treated with inotuzumab ozogamicin given in combination with rituximab was previously reported.

To assess safety, pharmacokinetics, and preliminary efficacy of inotuzumab ozogamicin in combination with rituximab in Japanese patients with relapsed or refractory B-cell NHL.

Patients were eligible if they had both CD20 and CD22-positive B-cell NHL, which had not responded to or progressed after 1 or 2 therapies. At least 1 prior regimen had to contain rituximab, and patients could not have progressed under treatment or within 6 months of start of rituximab-containing therapy. Patients received 375 mg/m² of rituximab on Day 1 followed by 1.8 mg/m² of inotuzumab ozogamicin on Day 2 of each 28-day cycle for up to 8 cycles, provided that there was no disease progression or intolerable toxicity. Adverse events (AEs) were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0 in patients who received at least 1 dose of the study drug. Objective response rate (ORR) was evaluated according to the International Response Criteria for NHL.

Ten patients were enrolled and treated with 1.8 mg/m² of inotuzumab ozogamicin in combination with rituximab for a median of 4 cycles. Median age was 60.5 (range 46 – 74), 50% were male, and 50% each had 1 and 2 prior chemotherapy regimens. Six patients were diagnosed as having follicular lymphoma (FL), 2 patients as mantle cell lymphoma (MCL), 1 patient each as diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma. Grade 3 or 4 treatment-emergent AEs reported in >20% of the patients were thrombocytopenia (70%), neutropenia (50%), leukopenia (30%), and lymphopenia (30%). AEs resulting in treatment discontinuation were neutropenia (30%) and hyperbilirubinemia (20%). No serious AEs were observed. An ORR of 80% (95% CI, 44 – 98%) was observed in the 10 patients treated. Five out of 6 patients with FL and 1 patient with MALT lymphoma achieved a complete response (CR). One out of 2 patients with MCL achieved unconfirmed CR (CRu), and 1 patient with FL attained partial response (PR). Progression-free survival (PFS) rate at 52 weeks was estimated to be 89% (95% CI, 43 – 98). ORR was 88% (95% CI, 47 – 100%) in the 8 patients that received at least 2 doses of the study drug and had at least 1 post-baseline tumor assessment (5 FL, 2 MCL, and 1 MALT lymphoma). Results of the pharmacokinetics assessment will be presented at the meeting.

The combination of inotuzumab ozogamicin plus rituximab has a safety profile similar to that previously reported for inotuzumab ozogamicin as a single agent, with hematologic AEs being the most frequent toxicities. The preliminary but encouraging evidence of clinical activity in Japanese patients with relapsed or refractory B-cell NHL warrants continued clinical development of this combination.

Tokushige:Pfizer Japan Inc.: Employment. Ono:Pfizer Japan Inc.: Employment. Vandendries:Pfizer Inc.: Employment, Equity Ownership.