Clinical efficacy and safety of the BAT1706 (proposed bevacizumab biosimilar) compared with reference bevacizumab in patients with advanced nonsquamous NSCLC: A randomized, double-blind, phase III study.

Abstract

9041 Background: A Randomized, Double-blind, Phase III Study was conducted to confirm clinical similarity between BAT1706, a proposed biosimilar to reference bevacizumab, and EU-bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Methods: Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (Arm A) or EU-bevacizumab plus paclitaxel and carboplatin (Arm B) given three weeks for 6 cycles, followed by maintenance therapy with BAT1706 or EU- bevacizumab. The primary endpoint was overall response rate at Week 18 (ORR18). Secondary endpoints included ORR at Week 6 and 12, best ORR, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results: A total of 651 patients were randomized: BAT1706 (n = 325) or EU- bevacizumab (n = 326). In total, 649 randomized patients (BAT1706 (n = 325) or EU- bevacizumab (n = 324)) received at least one cycle of combination treatment. The median duration of therapy was 29.1 weeks (ranging from 3.0 to 62.1 weeks) in the Arm A and 27.0 weeks (ranging from 3.0 to 53.9 weeks) in the Arm B. The extent of exposure to BAT1706 and EU- bevacizumab was similar between these two arms. Overall, the proportion of patients achieving an ORR by Week 18 was comparable across Arm A and B (48.0% and 44.5%). The ORR risk ratio of 1.08 with 90% CI (0.94, 1.24) and the ORR risk difference of 0.03, with 95% CI (-0.04, 0.11) were within pre-specified equivalence margin. In addition, the multivariate-adjusted risk ratio was 1.07, with a 90% CI (0.93, 1.22). The ORR18 risk difference between BAT1706 and EU- bevacizumab was 0.03, with the 2-sided 95% CI (-0.04, 0.11) that fell entirely within pre-specified equivalence margin. In addition, the multivariate-adjusted risk difference was 0.03, with a 95% CI (-0.04, 0.11). The hazard ratio stratified for time to PFS was 0.915 and the PFS rate at 12 months was 20.7% versus 21.8%. At the end of the study, there were no significant differences between both the treatments. The incidence of treatment-emergent adverse events (TEAEs) and study drug-related TEAEs was similar between these two arms. Overall, the safety profiles of BAT1706 were consistent with that of EU- bevacizumab, no new safety signals or noticeable trends were observed. The mean serum concentrations were comparable between BAT1706 and EU- bevacizumab over the entire sampling interval both in pre-dose and post-dose. The incidence of positive anti-drug antibodies results was low (≤5%) and decreased over time in both treatment arms. No patient was detected to have positive neutralizing anti-drug antibody result during the study. Conclusions: BAT1706 demonstrated clinical equivalence to reference EU-bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity. Clinical trial information: NCT03329911.

Physicochemical and Functional Similarity Assessment Between Proposed Bevacizumab Biosimilar BAT1706 and Reference Bevacizumab

“…In a Phase I trial in healthy volunteers, BAT1706 was shown to be highly similar to EU/US-bevacizumab in terms of PK equivalence (90% CI for the AUC 0–inf was 99–112% for BAT1706 versus EU-bevacizumab and 97–110% for BAT1706 vs US-bevacizumab), safety (no significant adverse events attributable to BAT1706, as compared to EU/US-bevacizumab), and immunogenicity (no anti-drug antibody positive result was reported for any subject) [ 19 ]. BAT1706 has also been evaluated in a Phase III trial in patients with advanced nonsquamous non-small-cell lung carcinoma, where clinical equivalence to EU-bevacizumab was demonstrated in terms of efficacy (48% patients achieving overall response rate in BAT1706 arm and 44.5% in EU-bevacizumab arm; progression-free survival at 12 months was 20.7% and 21.8%, respectively), safety (incidence of treatment-emergent adverse events [TEAEs] and study drug-related TEAEs was similar between BAT1706 and EU-bevacizumab arms), PK (mean serum concentrations were comparable between BAT1706 and EU-bevacizumab), and immunogenicity (no positive neutralizing anti-drug antibodies in any patient) [ 20 ].…”

Clinical Benefit, Price, and Uptake for Cancer Biosimilars vs Reference Drugs in China

“…were uncertain risk, 37,41,44,52,62 and 2 (5.1%) were high risk. 56,61 Of the cohort studies, 4 (40.0%)…”

“…Of those, 37 RCTs were published in journals, 32-35,37-50,52-70 1 was reported in ClinicalTrials.gov, 51 and 1 was reported in an NMPA review. 36 Of the 39 RCTs, 18 studied bevacizumab biosimilars, [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] 12 studied rituximab biosimilars, 50-61 and 9 studied trastuzumab biosimilars. [62][63][64][65][66][67][68][69][70] Of the RCTs, 33 were prespecified as equivalence designs, [32][33][34][35][36][37][38][39][40][41][42][43][44][46][47][48][49][50][51][52][53][54][55]58,60,…”

“…The median duration for assessing the primary efficacy end points was 18 weeks (IQR, 18-21 weeks) for bevacizumab biosimilars, 23 weeks (IQR, 23-24 weeks) for rituximab biosimilars, and 24 weeks (IQR, 23-24 weeks) for trastuzumab biosimilars. Thirty-four RCTs reported the incidence of antidrug JAMA Network Open | Health Policy antibodies, [32][33][34][35][36][37][38][39][40][41][42][43][45][46][47][48][49][50][51][52][53][54][55][56][58][59][60][62][63][64][66][67][68]70 and 28 reported the incidence of neutralizing antibodies. [32][33][34][35][36][37][38][39][40][41][42][43][47][48][49][50][51][52][53]…”

“…Benefit, Price, and Uptake for Cancer Biosimilars vs Reference Drugs in China antibodies, [32][33][34][35][36][37][38][39][40][41][42][43][45][46][47][48][49][50][51][52][53][54][55][56][58][59][60][62][63][64][66][67][68]70 and 28 reported the incidence of neutralizing antibodies. [32][33][34][35][36][37][38][39][40][41][42][43][47][48][49][50][51][52][53][54][55]58,[62]…”