Conference Coverage

Phase 3 study confirms biosimilarity of PF-05280586 with rituximab



– The potential rituximab biosimilar drug PF-05280586 showed efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics similar to those of rituximab at up to 26 weeks in a randomized phase 3 study of treatment-naive patients with CD20-positive low tumor burden follicular lymphoma (LTB-FL).

Dr. Jeff Sharman of Willamette Valley Cancer Institute and Research Center, Springfield, Ore. Sharon Worcester/MDedge News

Dr. Jeff Sharman

The primary endpoint of overall response rate at 26 weeks was 75.5% in 196 patients randomized to receive PF-05280586, and 70.7% in 198 patients who received a rituximab reference product sourced from the European Union (MabThera; rituximab‑EU), Jeff Sharman, MD, reported at the annual meeting of the American Society of Hematology.

“This resulted in a difference between the two arms of 4.66%,” said Dr. Sharman of Willamette Valley Cancer Institute and Research Center, Springfield, Ore.

The 95% confidence interval for this difference ... was entirely contained within the prespecified equivalence margin, he said.

“Depth of response was a key secondary endpoint, and rates of complete response were 29.3% and 30.4%, respectively,” he said, noting that rates of partial response, stable response, and progressive disease were also similar between the two study arms.

Estimated 1-year progression-free survival (PFS) rates were also highly similar at 76.4% and 81.2% in the PF-05280586 and rituximab-EU arms.

Rapid depletion in CD19-positive B-cell counts was observed in both groups after initial dosing, with recovery by week 39 and a sustained increase until the end of week 52.

Treatment-emergent adverse events (TEAEs) occurred in 78.6% vs. 72.1% of patients in the PF‑05280586 vs. rituximab‑EU arms, respectively, and the rates of serious adverse events and grade 3 events were similar in the groups, as were rates of infusion interruptions or infusion-related reactions (IRRs), Dr. Sharman said.

IRRs occurred in about 25% of patients in each arm, and most were grade 1 or 2. Grade 3 IRRs occurred in 2.6% vs. 0.5% of patients in the groups, respectively, and no grade 4 IRRs occurred.

Rates of anti-drug antibodies were also similar in the two groups, as were serum drug concentrations – regardless of anti-drug antibody status, he noted.

Study subjects were adults with a mean age of 60 years and histologically confirmed CD20-positive grade 1-3a follicular lymphoma with no prior rituximab or system therapy for B-cell non-Hodgkin lymphoma (NHL). They had Ann Arbor disease stages II (26.9%), III (44.2%) or IV (28.9%), ECOG performance status of 0-1, and at least 1 measurable disease lesion identifiable on imaging.

Risk level as assessed by the Follicular Lymphoma International Prognostic Index–2 was low in 28.4%, medium in 66%, and high in 5.6% of patients.

Treatment with each agent was given at intravenous doses of 375 mg/m2 weekly for 4 weeks at days 1, 8, 15, and 22.

PF-05280586 is being developed by Pfizer, and in this 52-week double-blind study – the largest study to date of the early use of the potential rituximab biosimilar in patients with previously untreated CD20-positive LTB-FL – the primary endpoint was met, demonstrating its therapeutic equivalence with rituximab-EU for overall response rate at week 26, Dr. Sharman said.

“These results therefore confirm the biosimilarity of PF-05280586 with rituximab-EU,” he concluded.

Of note, the reporting of these findings comes on the heels of the first Food and Drug Administration approval of a biosimilar rituximab product for the treatment of NHL; Celltrion’s product Truxima (formerly CT-P10), a biosimilar of Genentech’s Rituxan (rituximab), was approved Nov. 28 to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.

The PF-0528056 study was sponsored by Pfizer. Dr. Sharman has been a consultant for, and/or received research funding and honoraria from Acerta, Pharmacyclics (an AbbVie Company), Pfizer, TG Therapeutics, Abbvie, and Genentech.

SOURCE: Sharman J et al. ASH 2018: Abstract 394.

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