FDA Schedules ODAC Meeting for Rituximab Biosimilar

Woosung Kee

The FDA has scheduled an Oncologic Drugs Advisory Committee (ODAC) hearing for October 10, 2018, to discuss a biologics license application (BLA) for CT-P10, a proposed biosimilar to rituximab (Rituxan).

The panel will discuss the benefits and risks of CT-P10 and issue nonbinding recommendations for the FDA to consider when making its approval decision. Celltrion, the company developing CT-P10 with Teva Pharmaceutical Industries, reported in a press release that CT-P10 is already approved in over 47 countries.

“We are fully committed to preparing for this advisory committee meeting and look forward to the discussion about CT-P10,” Woosung Kee, CEO of Celltrion, said in a statement. “The development of biosimilars is of great importance in the field of oncology, and has the potential to enrich our therapeutic arsenal and to increase accessibility to therapies for patients at an affordable price.”

Data were presented at the 2018 ASCO Annual Meeting for a phase III trial demonstrating noninferiority for frontline CT-P10 compared with rituximab when combining the agents with CVP (cyclophosphamide, vincristine, prednisolone) chemotherapy in patients with advanced-stage follicular lymphoma (FL). Pharmacokinetics, pharmacodynamics, and safety were also comparable between the 2 agents.

The study included 140 patients with newly diagnosed advanced FL who were randomized in a 1:1 ratio to CT-P10 or rituximab (375 mg/m²) plus CVP every 3 weeks over 8 cycles (induction period). Following induction, there was a 2-year maintenance period during which patients received CT-P10 or rituximab monotherapy based on their initial randomization.

Patient characteristics were well balanced between the 2 arms. Overall, the median patient age was 57.5 years (range, 26-85), 55% of patients were female, and 45% were male. Almost three-fourths of patients were white. Seventy percent of patients had grade 2 or higher disease, with 40.7% at Ann Arbor stage III and 59.3% at Ann Arbor stage IV. The ECOG performance scores were 0 (65%), 1 (33.6%), and 2 (1.4%). Bone marrow involvement was reported in 55.7% of patients.

Sixty-two patients in each arm completed the induction phase. There were 16 discontinuations overall, resulting from progressive disease (n = 5), adverse event (n = 5), withdrawal of consent (n = 3), investigator decision (n = 2), and patient death (n = 1).

The overall response rate (ORR) over 8 cycles was 97.0% with CT-P10 compared with 92.6% with rituximab. The ORR in the CT-P10 group comprised a partial response (PR) rate of 57.6%, a CR rate of 9.1%, and an unconfirmed CR (CRu) rate of 30.3%. In the rituximab arm, the PR rate was 58.8%, the CR rate was 11.8%, and the CRu rate was 22.1%.

Also for the induction period, B-cell kinetics were similar between the 2 arms. Regarding immunogenicity, 4.3% of patients in the CT-P10 arm had positive antidrug antibody results compared with 2.9% in the rituximab arm.

Safety was comparable, with all-grade treatment-emergent adverse events (TEAEs) occurring in 82.9% and 80.0% of patients in the biosimilar and rituximab arms, respectively. The rates of serious TEAEs were 22.9% versus 12.9%, respectively.

Adverse events of special interest occurred at similar rates, including infusion-related reaction (21.4% with CT-P10 versus 24.3% with rituximab), infection (31.4% vs 37.1%), neutropenia (34.3% vs 22.9%), and malignancy (0 vs 1.4%). There was 1 patient death in the biosimilar group and none in the rituximab group.

Rituximab has approved indications for FL, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia.

Kim WS, Jurczak W, Sancho J-M, et al. Double-blind, randomized phase 3 study to compare efficacy and safety of the biosimilar CT-P10 to rituximab combined with CVP therapy in patients with previously untreated advanced-stage follicular lymphoma. J Clin Oncol. 2018;36 (suppl; abstr 7532).