Heritage, a phase III safety and efficacy trial of the proposed trastuzumab biosimilar, Myl-1401O vs trastuzumab

Date

09 Oct 2016

Session

Breast cancer, metastatic

Presenters

Hope Rugo

Citation

Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435

Authors

H. Rugo1, A. Barve2, C.F. Waller3, M. Bronchud4, J. Herson5, J. Yuan2, A. Manikhas6, I. Bondarenko7, G. Mukhametshina8, G. Nemsadze9, J.D. Parra10, M.L.T. Abesamis-Tiambeng11, K. Baramidze12, C. Akewanlop13, I. Vynnychenko14, V. Sriuranpong15, G. Mamillapalli16, S. Ray17, E.P. Yanez Ruiz18, E. Pennella2

Author affiliations

  • 1 Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 2 Global Clinical Research, Mylan, 15317 - Canonsburg/US
  • 3 Department Of Haematology, Oncology And Stem Cell Transplantation, University Medical Centre Freiburg and Faculty of Medicine, - - Freiburg/DE
  • 4 Clinical Oncology, Instituto Universitario USP Dexeus, 08028 - Barcelona/ES
  • 5 Center For Clinical Trials, Johns Hopkins Bloomberg School of Public Health, 21205 - Baltimore/US
  • 6 City Clinical Oncology Dispensary, City Clinical Oncology Center, 198255 - St. Petersburg/RU
  • 7 Department Of Oncology, Radiodiagnosis And Radiotherapy, Dnipropetrovsk Municipal Clinical Hospital #4, 49102 - Dnepropetrovsk/UA
  • 8 Regional Clinical Oncological Center, Kazan Clinical Oncology Center, 420029 - Kazan/RU
  • 9 Oncology, Institute of Clinical Oncology, 0159 - Tbilisi/GE
  • 10 Oncology, St. Luke's Medical Center, - - Taguig City/PH
  • 11 Cancer Institute, Cardinal Santos Medical Center, 1502 - Manila/PH
  • 12 -, Golden Fleece 21 Century Health House Ltd, 0144 - Tbilisi/GE
  • 13 Department Of Medicine, Medical Oncology Unit, Siriraj Hospital, Mahidol University, 10700 - Bangkok/TH
  • 14 Oncology, Sumy Regional Oncology Center, 40005 - Sumy/UA
  • 15 Department Of Medicine, Medical Oncology Unit, King Chulalongkorn Memorial Hospital, 10330 - Bangkok/TH
  • 16 City Cancer Center, City Cancer Center, 520002 - Vijayawada/IN
  • 17 -, Curie Manavata Cancer Centre, 422001 - Nashik/IN
  • 18 -, Instituto Clinico Oncológico del Sur, 01745 - Temuco/CL
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Resources

Background

Globally accessible alternatives of trastuzumab are a critical need. We evaluated MYL-1401O, a proposed trastuzumab biosimilar as first-line treatment for HER2+ metastatic breast cancer (MBC).

Methods

Heritage is a double-blind, randomized clinical trial designed to evaluate comparative efficacy and safety of MYL-1401O vs Herceptin. Centrally confirmed, measurable HER2+ MBC patients (pts) were randomized to receive either MYL-1401O or Herceptin with docetaxel or paclitaxel for a minimum of 8 cycles, and then Trastuzumab until progression. The primary endpoint was overall response (ORR) at Week 24 by blinded central evaluation using RECIST 1.1. Secondary endpoints include progression free survival (PFS), overall survival (OS), and safety. A sample size of 456 pts was calculated to demonstrate equivalence in ORR at Week 24 for MYL-1401O vs Herceptin, defined as a 90% confidence interval (CI) for the ratio of best ORR within the equivalence margin (0.81, 1.24).

Results

500 pts were randomized, 458 were evaluable for efficacy. 44% had hormone receptor positive MBC, 84% received docetaxel. Week 24 ORR was 69.6% for MYL-1401O compared to 64% for Herceptin. The ratio of ORR was 1.09; both 90% CI (0.974-1.211) and 95% CI (0.954-1.237) were within the pre-defined equivalence margin. Investigator assessment of PFS with a minimum follow up of 48 weeks was not statistically different for MYL-1401O vs. Herceptin, HR 0.96 (95% CI: 0.730, 1.261; log rank p: 0.764), with a median Kaplan Meier PFS of 11.1 months in both arms. Median OS has not been reached; OS at 48 weeks is 89.1% and 85.1% for MYL-1401O and Herceptin respectively. Safety was comparable; serious adverse events (primarily neutropenia related) occurred in 39.3% (MYL-1401O) vs 37% (Herceptin), with 6 and 4 fatal events in MYL-1401O and Herceptin arms respectively. At week 48 the mean LVEF was similar with a decrease from baseline of -1.3 and -1.2.

Conclusions

MYL-1401O is equivalent to Herceptin, given in combination with a taxane as first line therapy for MBC, as measured by ORR. At 48 weeks no significant difference was noted for PFS or OS. Safety, immunogenicity and Pop PK data were comparable.

Clinical trial identification

EudraCT No: 2011-001965-42

Legal entity responsible for the study

Mylan GmbH

Funding

Mylan GmbH

Disclosure

H. Rugo: I have not received any funding personally. However, funding for specific research studies that I lead is provided to my instt from Genentech/Roche. I have received only travel support to speak at a meeting from Genentech/Roche. A. Barve: I am a Mylan full-time employee and have stock in Mylan. C.F. Waller: I am a member of Mylan advisory board. M. Bronchud: No stock ownership but I have a membership of advisory board for Mylan. J. Yuan: I am an employee of Mylan. In addition, I have a financial relationship with my employer in the form of stock options, consulting/advisory role and recipient of travel/accommodation expenses. M.L.T. Abesamis-Tiambeng: Consulting/advisory role and on speakers bureau: Boehringer-Ingelheim, Roche, MSD; Research funding received from: Roche, Pfizer, Mylan, AB Science, Cell-Trion, Amgen; Travel expenses/ accommodation reimbursements received from: Merck-Serono. C. Akewanlop: I have been the principal investigator in clinical trials funded by Mylan, Roche, AstraZeneca and Novartis. E. Pennella: I am Mylan employee and I have stocks of Mylan. All other authors have declared no conflicts of interest.

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