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 endpointITTPP
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) 
Primary endpointITTPP
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.