Efficacy, Safety and Immunogenicity of MB02 (Bevacizumab Biosimilar) versus Reference Bevacizumab in Advanced Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study (STELLA)

Dmytro Trukhin, Elena Poddubskaya, Zoran Andric, Tamta Makharadze, Ravi Shankar Bellala, Chaiyut Charoentum, Eduardo P Yañez Ruiz, Andrea Fulop, Irfhan Ali Hyder Ali, Kostas Syrigos, Nuran Katgi, Yamil Alonso Lopez Chuken, Ilieva Rumyana, Jasmin Reyes-Igama, Rita de Cassia Costamilan, Ana Del Campo García, Amalia Florez, Alexandra Paravisini, Susana Millan, STELLA Investigators, Luiz Henrique de Lima Araujo, Carla Maria de Oliveira Ferreira, Helio Pinczowski, Maria Marcela Fernandes Monteiro, Assen Dudov, Janeta Syrova, Francisco Javier Orlandi Jorquera, Carlos Eduardo Gallardo Arenada, Christian Lorenzo Caglevic Medina, Davit Giorgadze, Nino Mchedlidze, Vladimer Kuchava, Tamar Melkadze, Amiran Matitashvili, Nana Chikhladze, Epaminodas Samantas, Theodoros Kontakiotis, Beatrix Balint, Balazs Medgyasszay, Eszter Csanky, Shailesh Arjun Bondarde, Lovenish Goyal, Ajay Sharma, Baijumon Balan, Prabrajya Narayan Mohapatra, Kaushalkumar Babubhai Patel, Sachin Sharadchandra Hingmire, Mithun Satish Shah, Kartikeya Jain, Ashish Agrawal, Prashant Kumbhaj, Asis Mukhopadhyay, Paul Khoueiry, Suhana Yusak, Yong Kek Pang, Voon Pei Jye, Prathepamalar Yehgambaram, Fuad Bin Ismail, Gokula Kumar Appalanaido, Feliciano Barron Barron, Ma Noemi Uy, Felycette Gay Martinez-Lapus, Maria Belen Tamayo, Jennifer Sandoval-Tan, Jamela Anne Osorio Sanchez, Christina G Galvez, Josephine Contreras-Tolentino, Evgeny Ledin, Daniil Stroyakovskiy, Igor Kudryavtsev, Vladimir Vladimirov, Evgeniy Gotovkin, Marina Shomova, Guzel Mukhametshina, Igor Lifirenko, Nina Karaseva, Marina Nechaeva, Anna Tarasova, Alexander Luft, Lyudmila Kuzina, Marina Petrovic, Milan Rancic, Borjan Zaric, Manoch Buranachokphaisan, Sarayut Lucien Geater, Ekkapong Tharavichitkul, Mahmut Gumus, Igor Bondarenko, Yaroslav Shparyk, Serhii Shevnia, Iryna Lytvyn, Oleksii Kolesnik, Yevhen Hotko, Ivan Sinielnikov, Hryhoriy Adamchuk, Grygorii Ursol, Oleksandr Ivashchuk, Yuriy Ostapenko, Tetiana Popovska, Dmytro Trukhin, Elena Poddubskaya, Zoran Andric, Tamta Makharadze, Ravi Shankar Bellala, Chaiyut Charoentum, Eduardo P Yañez Ruiz, Andrea Fulop, Irfhan Ali Hyder Ali, Kostas Syrigos, Nuran Katgi, Yamil Alonso Lopez Chuken, Ilieva Rumyana, Jasmin Reyes-Igama, Rita de Cassia Costamilan, Ana Del Campo García, Amalia Florez, Alexandra Paravisini, Susana Millan, STELLA Investigators, Luiz Henrique de Lima Araujo, Carla Maria de Oliveira Ferreira, Helio Pinczowski, Maria Marcela Fernandes Monteiro, Assen Dudov, Janeta Syrova, Francisco Javier Orlandi Jorquera, Carlos Eduardo Gallardo Arenada, Christian Lorenzo Caglevic Medina, Davit Giorgadze, Nino Mchedlidze, Vladimer Kuchava, Tamar Melkadze, Amiran Matitashvili, Nana Chikhladze, Epaminodas Samantas, Theodoros Kontakiotis, Beatrix Balint, Balazs Medgyasszay, Eszter Csanky, Shailesh Arjun Bondarde, Lovenish Goyal, Ajay Sharma, Baijumon Balan, Prabrajya Narayan Mohapatra, Kaushalkumar Babubhai Patel, Sachin Sharadchandra Hingmire, Mithun Satish Shah, Kartikeya Jain, Ashish Agrawal, Prashant Kumbhaj, Asis Mukhopadhyay, Paul Khoueiry, Suhana Yusak, Yong Kek Pang, Voon Pei Jye, Prathepamalar Yehgambaram, Fuad Bin Ismail, Gokula Kumar Appalanaido, Feliciano Barron Barron, Ma Noemi Uy, Felycette Gay Martinez-Lapus, Maria Belen Tamayo, Jennifer Sandoval-Tan, Jamela Anne Osorio Sanchez, Christina G Galvez, Josephine Contreras-Tolentino, Evgeny Ledin, Daniil Stroyakovskiy, Igor Kudryavtsev, Vladimir Vladimirov, Evgeniy Gotovkin, Marina Shomova, Guzel Mukhametshina, Igor Lifirenko, Nina Karaseva, Marina Nechaeva, Anna Tarasova, Alexander Luft, Lyudmila Kuzina, Marina Petrovic, Milan Rancic, Borjan Zaric, Manoch Buranachokphaisan, Sarayut Lucien Geater, Ekkapong Tharavichitkul, Mahmut Gumus, Igor Bondarenko, Yaroslav Shparyk, Serhii Shevnia, Iryna Lytvyn, Oleksii Kolesnik, Yevhen Hotko, Ivan Sinielnikov, Hryhoriy Adamchuk, Grygorii Ursol, Oleksandr Ivashchuk, Yuriy Ostapenko, Tetiana Popovska

Abstract

Background: MB02 (bevacizumab biosimilar) showed similar structural, functional, and pharmacokinetic properties to reference bevacizumab (Avastin®; EU-bevacizumab).

Objectives: To confirm clinical similarity between MB02 and EU-bevacizumab, a comparability study was undertaken in the first-line treatment of stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC).

Patients and methods: This multinational, double-blind, randomized, phase III study (STELLA) compared MB02 or EU-bevacizumab (15 mg/kg) administered with chemotherapy (paclitaxel 200 mg/m2 and carboplatin AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18), followed by MB02/EU-bevacizumab in blinded monotherapy until disease progression, unacceptable toxicity, death, withdrawal of consent or end of study (Week 52). The primary efficacy endpoint was objective response rate (ORR) evaluated by an independent radiological review committee (IRC) at Week 18 (intent-to-treat population). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and immunogenicity.

Results: A total of 627 subjects were randomized 1:1 to MB02 (n = 315) or EU-bevacizumab (n = 312). ORR, assessed by the IRC at Week 18, was comparable in MB02 (40.3%) and EU-bevacizumab (44.6%) groups. ORR risk ratio of 0.910 (90% CI 0.780 to 1.060; 95% CI 0.758 to 1.092) and ORR risk difference of -4.02 (90% CI -10.51 to 2.47; 95% CI -11.76 to 3.71) were within the similarity predefined margins. There were no significant differences between MB02 and EU-bevacizumab groups in median PFS (36.0 vs 37.3 weeks, respectively; HR 1.187; 95% CI 0.98 to 1.44) and median OS (not achieved; HR 1.108; 95% CI: 0.83 to 1.49) at the end of study. The safety profile of MB02 and EU-bevacizumab regarding nature, frequency and severity of the adverse events (AE) was comparable. The most frequent grade ≥3 investigational-product-related AEs were hypertension and anemia, with a difference between treatment groups of <5%. Anti-drug antibodies (ADA) and neutralizing ADA (NAb) incidence were similar in both treatment groups.

Conclusion: MB02 demonstrated similar efficacy to EU-bevacizumab, in combination with carboplatin and paclitaxel, in subjects with advanced non-squamous NSCLC, with comparable safety and immunogenicity profiles.

Clinical trial registration: EudraCT No. 2017-001769-26; ClinicalTrials.gov: NCT03296163.

Conflict of interest statement

SM, AP, AF and ADCG are employees at mAbxience Research SL.

All the other authors declared that they have no conflicts of interest.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Subject disposition
Fig. 2
Fig. 2
Kaplan–Meier plots of (a) progression-free survival, (b) overall survival, (c) duration of response and (d) time to overall response in the intention-to-treat population
Fig. 2
Fig. 2
Kaplan–Meier plots of (a) progression-free survival, (b) overall survival, (c) duration of response and (d) time to overall response in the intention-to-treat population

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Source: PubMed

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