Research Demonstrates Efficacy and Safety of Trastuzumab Biosimilar SB3

A study presented at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO) demonstrates that SB3, a proposed biosimilar to trastuzumab (TRZ), has comparable efficacy, safety, immunogenicity, and pharmacokinetics (PK) to the reference product based on the breast pathological complete response (bpCR), which was the primary endpoint.

The phase 3, double-blind, randomized, parallel-group, multicenter study, sponsored by Samsung Bioepis, sought to demonstrate the comparable efficacy of SB3 (which has an identical primary amino acid sequence to TRZ) and TRZ in terms of bpCR when the products are used in neoadjuvant settings in women who have either epidermal growth factor receptor 2—positive early breast cancer or locally advanced breast cancer.

Patients, 18 to 65 years of age and newly diagnosed with stage II to III primary breast cancer, received either SB3 or the reference product for 8 treatment cycles, which were given concurrently with chemotherapy. The patients then underwent surgery and a subsequent 10 cycles of either SB3 or TRZ.

The researchers defined bpCR rate as the primary endpoint of the study, which comprised 403 patients per arm. The study analyzed efficacy in a per-protocol set (PPS), comprising those who had completed neoadjuvant therapy and surgery without any pre-specified major deviations from protocol, and further considered a full-analysis set to provide supportive data.

Drawing upon several published TRZ studies as a guideline, the researchers set equivalence margins in the PPS at a 90% confidence interval (CI) of the ratio of bpCR rates for SB3 and TRZ, or a 95% CI of the difference of bpCR rates for the 2 products. Secondary endpoints for the study included total pathologic complete response (tpCR), overall response rate (ORR), event-free survival, PK equivalence, immunogenicity, and safety.

The researchers found that, after adjusting results by hormone receptor status, disease stage, and region, the adjusted bpCR ratio for the PPS was 1.259 (90% CI, 1.112-1.426), a value which falls within the pre-defined margin of 0.785 to 1.546. The adjusted difference was 10.7% (95% CI, 4.13%-17.26%), with the lower margin contained within and the upper margin falling outside the pre-defined margin (-13%-13%). The tpCR results were reflective of the bpCR findings, with an adjusted PPS ratio of 1.315 (90% CI, 1.137-1.520). Results for ORR also bore out bpCR results, with an adjusted ratio for the PPS at 1.055 (90% CI, 1.023-1.088).

Additionally, the study data demonstrate comparable safety between SB3 and TRZ, with neutropenia, alopecia, and nausea representing the most commonly reported adverse effects in both study arms. PK data demonstrated equivalent steady-state trough levels. Finally, immunogenicity was comparable between the 2 groups up to cycle 9 of treatment, with positive anti-drug antibody results reported for 3 patients in the group receiving SB3 and none in the group receiving TZB.

While the report notes that complete safety and survival data will follow, the researchers concluded that SB3 and TZB had equivalent efficacy based on the ratio of bpCR rates, and that SB3 was both well tolerated and comparable to TZB in safety, immunogenicity, and PK.