Sergii Shevnya

BACKGROUND: CT-P16 is a candidate bevacizumab biosimilar. OBJECTIVE: This double-blind, multicenter, parallel-group, phase III study aimed to establish equivalent efficacy between CT-P16 and European Union-approved reference bevacizumab (EU-bevacizumab) in patients with metastatic or recurrent non-squamous non-small cell lung cancer (nsNSCLC). PATIENTS AND METHODS: ) and carboplatin (area under the curve 6.0; both for 4-6 cycles), as induction therapy. Patients with controlled disease after induction therapy continued with CT-P16 or EU-bevacizumab maintenance therapy. The primary endpoint was objective response rate (ORR) during the induction period. Time-to-event analyses, pharmacokinetics, safety, and immunogenicity were also evaluated. Results obtained after 1 year of follow-up are presented. RESULTS: Overall, 689 patients were randomized (CT-P16, N = 342; EU-bevacizumab, N = 347). ORR was 42.40% (95% confidence interval [CI] 37.16-47.64) and 42.07% (95% CI 36.88-47.27) for CT-P16 and EU-bevacizumab, respectively. The risk difference (0.40 [95% CI - 7.02 to 7.83]) and risk ratio (1.0136 [90% CI 0.8767-1.1719]) for ORR fell within predefined equivalence margins (- 12.5 to + 12.5%, and 0.7368 to 1.3572, respectively), demonstrating equivalence between CT-P16 and EU-bevacizumab. Median response duration, time to progression, progression-free survival, and overall survival were comparable between treatment groups. Safety profiles were similar: 96.2% (CT-P16) and 93.0% (EU-bevacizumab) of patients experienced treatment-emergent adverse events. Pharmacokinetics and immunogenicity were comparable between groups. CONCLUSIONS: Equivalent efficacy and similar pharmacokinetics, safety, and immunogenicity support bioequivalence of CT-P16 and EU-bevacizumab in patients with nsNSCLC. TRIAL REGISTRATION NUMBER: NCT03676192.

Abstract Background: CT-P16 is a proposed biosimilar to FDA approved reference bevacizumab (BV), namely Avastin®. This trial (NCT03676192) compared the efficacy and safety of CT-P16 and BV in patients with metastatic or recurrent non-squamous NSCLC. Methods: This double blind, randomized, multicenter study randomly assigned patients to CT-P16 or BV with carboplatin and paclitaxel, up to 6 cycles (Induction Period), followed by maintenance CT-P16 or BV monotherapy until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) during the Induction Period. ORR includes complete or partial responses based on RECIST v1.1 assessed by an independent reviewer. Secondary endpoints were Quality of life (QoL), PK, safety, and immunogenicity. Results: A total of 689 patients were randomized (CT-P16: 342, BV: 347). The baseline characteristics were well balanced. ORRs were similar between the two treatment arms and the 90% confidence intervals (CIs) for the risk ratio estimate (0.7368, 1.3572) and 95% CIs for risk difference estimate (±12.5%) were within the equivalence margin in both ITT (intent-to-treat) and PP (per-protocol) sets. QoL results (QLQ-C30 and QLQ-LC13) and PK parameter (Ctrough) were comparable between the two treatment arms. The overall incidence of treatment-emergent adverse events (TEAEs), serious AEs (TESAEs), AEs leading to discontinuation, and AEs leading to death was similar between the two treatment arms (96.2% vs. 92.4%, 19.4% vs. 20.1%, 15.1% vs. 14.5%, and 6.4% vs. 6.4% for the CT-P16 and BV treatment arm, respectively). The incidence of treatment-emergent anti-drug antibodies was comparable (14.2% vs. 16.0%). Conclusions: This study demonstrated that CT-P16 is equivalent to BV as measured by ORR in patients with metastatic or recurrent adenocarcinoma of the lung. Other endpoints including PK, QoL, safety and immunogenicity were comparable. Primary endpoint ITT PP CT-P16 (N=342) BV (N=347) CT-P16 (N=318) BV (N=303) Independent reviewer ORR (%) 95% CI 42.40 (37.16 - 47.64) 42.07 (36.88 - 47.27) 45.28 (39.81 - 50.75) 47.19 (41.57 - 52.82) Risk ratio estimate (90% CI) 1.0136 (0.8767, 1.1719) 0.9662 (0.8387, 1.1132) Risk difference estimate (%) (95% CI) 0.40 (-7.02, 7.83) -1.90 (-9.80, 6.00) Investigator ORR (%) 95% CI 43.86 (38.60 - 49.12) 39.19 (34.06 - 44.33) 46.54 (41.06 - 52.02) 43.89 (38.31 - 49.48) Risk ratio estimate (90% CI) 1.1234 (0.9683, 1.3032) 1.0648 (0.9209, 1.2313) Risk difference estimate (%) (95% CI) 4.87 (-2.53, 12.26) 2.90 (-4.99, 10.79) Citation Format: Yuichiro Ohe, Igor Bondarenko, Zoran Andric, Yuriy Ostapenko, Tudor Ciuleanu, Fedor Moiseenko, Tamta Makharadze, Sergii Shevnya, Alona Oleksiienko, Eduardo Yañez Ruiz, SungHyun Kim, KeumYoung Ahn, TaeHong Park, Sijin Park, JiEun Lee, MinJi Kim, Claire Verschraegen. Randomized phase III study comparing the efficacy and safety of CT-P16, a new biosimilar, to reference bevacizumab (Avastin®) in patients with metastatic or recurrent non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT551.