The FDA has accepted a biologics license application for the proposed bevacizumab biosimilar SB8.
The FDA has accepted a biologics license application (BLA) for the proposed bevacizumab (Avastin) biosimilar SB8, according to Samsung Bioepis, the developer of the agent.1
Phase III findings for SB8 were presented at the 2019 ESMO Congress, in which the biosimilar demonstrated similar efficacy in terms of best overall response rate (ORR) risk ratio compared with reference bevacizumab in patients with metastatic or recurrent nonsquamous non—small cell lung cancer (NSCLC).2
In the multicenter, double-blind, phase III trial (NCT02754882), 763 patients with metastatic or recurrent nonsquamous NSCLC were randomized 1:1 to receive SB8 (n = 379) or bevacizumab (n = 384) in combination with paclitaxel and carboplatin every 3 weeks, followed by either SB8 or bevacizumab as maintenance therapy. Treatment was given until disease progression, unacceptable toxicity, death, or 1 year from randomization of the last patient.
To be eligible for enrollment, patients had to be ≥18 years old, have an ECOG performance status of 0 or 1, have histologically confirmed metastatic or recurrent nonsquamous NSCLC, have ≥1 measurable lesion according to RECIST v1.1 criteria, and able to receive bevacizumab, carboplatin, and paclitaxel. Those who had diagnosis of small cell carcinoma of the lung or squamous cell carcinoma, EGFR mutations or ALK rearrangements, have an increased risk of bleeding, and history of first-line chemotherapy in the metastatic or recurrent setting were excluded from enrollment.
Baseline characteristics were similar between the 2 arms. The primary endpoint was best ORR by 24 weeks of chemotherapy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, pharmacokinetics, and immunogenicity. Additionally, risk ratio was analyzed in the full analysis set and the risk difference was determined in the per-protocol set.
Results showed that in the full analysis set, the best ORR was 47.6% and 42.8% with SB8 and reference bevacizumab, respectively, and the risk ratio was 1.11 (90% CI, 0.975-1.269), which was within the predefined equivalence margin (0.737-1.357).
In the per-protocol set, the best ORR was 50.1% with the biosimilar and 44.8% with bevacizumab. The risk difference was 5.3% (95% CI, −2.2%-12.9%], of which the lower margin was contained within and the upper margin was outside the predefined equivalence margin of (95% CI, −12.5%-12.5%).
Additionally, in the full analysis set, the median PFS was 8.50 months with SB8 compared with 7.90 months with reference bevacizumab, and the median OS was 14.90 months and 15.80 months, respectively. The median DOR with SB8 and bevacizumab was 5.60 months and 5.85 months, respectively.
Regarding safety, the overall incidence of treatment-emergent adverse events (TEAEs) was comparable between the 2 arms, at 92.1% with SB8 and 91.1% with reference bevacizumab. The TEAEs that occurred most frequently included alopecia, anemia, and nausea.
Ctrough and Cmax, as well as the incidence of overall antidrug antibodies (16.1% with SB8 vs 11.0% with bevacizumab), were comparable between both arms.
The BLA was submitted to the FDA in September 2019, Samsung Bioepis stated in a press release. Additionally, the European Medicines Agency accepted a Marketing Authorization Application in July 2019 for the bevacizumab biosimilar.
In June 2019, the FDA approved the bevacizumab biosimilar PF-06439535 (bevacizumab-bvzr; Zirabev), for the treatment of patients with metastatic colorectal cancer; unresectable, locally advanced, recurrent, or metastatic nonsquamous NSCLC; recurrent glioblastoma; metastatic renal cell carcinoma; and persistent, recurrent, or metastatic cervical cancer.