SB3 Shows Equivalence to Reference Trastuzumab in Phase 3 Study

A study newly published in the Journal of Clinical Oncology found that SB3, a proposed trastuzumab biosimilar being developed by Samsung Bioepis, demonstrated equivalence with European-sourced reference trastuzumab (Herceptin) in terms of breast pathologic complete response (bpCR) rate. Safety and immunogenicity for the 2 drugs were also similar.

The phase 3, randomized, double-blind, parallel-group, multicenter study, led by Xavier Pivot, MD, PhD, included patients aged 18 to 65 who had HER2-positive breast cancer. A total of 875 patients, the full analysis set (FAS), were randomized to receive either SB3 (n = 437) or the European-sourced reference Herceptin (n = 438). In total, 800 patients, the per protocol set (PPS) completed 8 cycles of neoadjuvant therapy and surgery (SB3, n = 402; reference, n = 398).

The primary endpoint of the study was the bpCR rate, defined as no histologic evidence of residual invasive tumor cells in the breast. Equivalence in terms of bpCR was declared if the 95% confidence interval (CI) of the ratio was within 0.785 to 1.546, or the 95% CI of the difference was within plus or minus 13%.

To assess safety, treatment-emergent adverse events (TEAEs) were assessed throughout the study. Blood samples were collected to assess pharmacokinetics (PK), and immunogenicity testing was performed to search for anti-drug antibodies (ADAs). At the time of data cutoff, the median follow-up durations were 337 days (range, 94 to 485 days) and 338 days (range, 24 to 475 days) in the SB3 and reference arms, respectively.

The researchers found the following with respect to efficacy:

• In the PPS, the proportions of patients achieving bpCR were 51.7% in the SB3 group and 42.0% in the reference group.
• The adjusted ratio of the bpCR rate in the PPS was 1.259 (95% CI, 1.085-1.460), which fell within the predefined equivalence margin. The adjusted difference was 10.70% (95% CI, 4.13%-17.26%), with the lower margin contained within and the upper margin outside of the predefined equivalence margin.
• In the FAS, the proportions of patients achieving bpCR were 49.0% in the SB3 group and 39.7% in the reference group.
• The adjusted ratio of the bpCR rate in the FAS was 1.243 (95% CI, 1.070-1.444).
• Overall, bpCR rates were higher in patients whose disease was estrogen receptor- and progesterone receptor-negative.

In terms of safety, the researchers report the following:

• In the neoadjuvant period, TEAEs were reported in 96.6% of patients in the SB3 group and 95.2% of the reference group.
• The most common TEAEs were neutropenia, alopecia, nausea, and leukopenia.
• TEAEs resulted in the death of 4 patients; none of the deaths were considered associated with the study drug.

With respect to PK, the researchers report that, in the PK population of 161 and 152 patients in the SB3 and reference arms, respectively, mean Ctrough profiles from cycle 3 to cycle 8 were similar. In terms of immunogenicity, up to cycle 9, 3 patients in the SB3 group were positive for ADAs. No patients in the reference group were ADA-positive for the same period.

The authors concluded that their data demonstrate the similarity of SB3 and the reference Herceptin. Patients may continue in a long-term extension of the study that will further monitor safety, event-free survival, and overall survival.

The FDA is currently reviewing Samsung Bioepis’ Biologics License Application for SB3, which has already been approved for marketing by the European Commission and the Republic of Korea.