MYL-1402O (MYL, proposed biosimilar to Avastin), has been developed and extensively characterized using state-of-the-art physicochemical and functional tests.
This was a multicenter, randomized, double blind, equivalence study to evaluate comparative efficacy and safety of MYL with Avastin in patients with Stage IV metastatic nsNSCLC. Patients received combination therapy of study treatment with carboplatin-paclitaxel (CP) up to 18 weeks (6 cycles) followed by 24 weeks (8 cycles) of monotherapy. The primary endpoint was overall response rate (ORR) at 18 weeks, based on RECIST 1.1 assessed by an independent review (IR) at any time point during the first 18 weeks. The equivalence margin for ratio of ORR (90% confidence interval [CI]) was 0.73, 1.36; and for difference in ORR (95% CI) was ± 12.5%. Sample size of 670 was determined adequate to evaluate equivalence. Key secondary endpoints included assessment of progression free survival (PFS), overall survival (OS), safety and immunogenicity up to 42 weeks.
671 patients (MYL: 337, Avastin: 334) were randomized. The ratio of ORR (90% CI) was 0.96 (0.83, 1.12) and the difference in ORR (95% CI) was -1.6 (-9.0, 5.9) between treatment arms. The CIs were within the pre-defined equivalence margin for ratio and difference in ORR. At Week 42, the median PFS (95% CI) in months for IR was 7.6 (7.0, 9.5) in MYL arm and 9.0 (7.2, 9.7) in Avastin arm (p = 0.0906); PFS for investigator assessment was 7.8 (7.0, 9.5) in MYL arm and 7.3 (7.0, 8.9) in Avastin arm (p = 0.4748). Median OS was not reached at 42 weeks; OS rate was 70.0% and 75.4% for MYL and Avastin, respectively (p = 0.1185). Safety was comparable between MYL and Avastin; Serious adverse events occurred in 17.6% vs. 16.7% with treatment related adverse events leading to death in 2.4% vs. 1.5% patients. The incidence of treatment emergent anti-drug antibodies (6.5% vs. 4.8%) was comparable between MYL and Avastin.
MYL is equivalent to Avastin, given in combination with CP, as measured by ORR. Other efficacy endpoints, safety and immunogenicity were comparable.
Clinical trial identification
EudraCT Number: 2015-005141-32.
Legal entity responsible for the study
Mylan Pharmaceuticals Pvt. Ltd Bangalore, India Mylan Pharmaceuticals Pvt. Ltd Bangalore, India Mylan Pharmaceuticals Pvt. Ltd Bangalore, India.
Mylan Pharmaceuticals Pvt. Ltd Bangalore, India.
M.A. Socinski: Research grant/Funding (institution), Research Support: Spectrum ; Speaker Bureau/Expert testimony, Research grant/Funding (self): AZ; Speaker Bureau/Expert testimony, Research grant/Funding (self): Genentech; Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Guardant; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Bayer; Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis. C. Waller: Advisory/Consultancy: Mylan Inc. T. Idris: Full/Part-time employment: Mylan Pharmaceuticals PvT Ltd. K. Beckmann: Full/Part-time employment: Mylan. A. Vishweswaramurthy: Full/Part-time employment: Biocon Biologics . S. Loganathan: Full/Part-time employment, Holds ESOP: Biocon. G. Ranganna: Full/Part-time employment: Mylan Pharmaceuticals Pvt Ltd. A. Barve: Full/Part-time employment: Mylan Inc. All other authors have declared no conflicts of interest.