67P - Efficacy and safety of trastuzumab biosimilar in HER2+ve metastatic breast cancer: A multicenter phase III study

Background

BP02 is a trastuzumab biosimilar in development. This study evaluated equivalence of BP02 to reference trastuzumab (RT: Herceptin-EU) in HER2+ve metastatic breast cancer (MBC).

Methods

In this randomized, double-blind, parallel-group, active-controlled, multicentric, phase 3 equivalence trial, we recruited women aged 18-75 yrs with histologically/ cytologically confirmed HER2+ve, locally recurrent or MBC with systemic metastasis, from 59 sites in India. Inclusion criteria were at least one measurable lesion (RECIST 1.1), ECOG performance status of ≤2, probable life expectancy of ≥18 mths, LVEF ≥55%, adequate renal, hepatic, and hematological functions. Exclusion criteria included contralateral breast cancer, cancer of any other site, metastases to brain and spinal cord; previous exposure to any prior therapy to metastatic disease; serious cardiac illness and known hypersensitivity to trastuzumab. We randomly allocated patients 1:1 stratified by ER and PR status to receive BP02 or RT (8mg/kg loading dose on day 1 of cycle 1, 6mg/kg on day 1 of cycles 2-8, each cycle lasting 3 wks) combined with docetaxel (75mg/m² on day 1 of cycles 1-8) [induction phase]. Participants with complete or partial response, or stable disease at end of induction phase continued the study drug until disease progression or treatment discontinuation [maintenance phase]. Participants and investigators were masked to treatment until study completion. The primary efficacy endpoint was objective response rate (ORR) as per RECIST 1.1. Results of induction phase are presented.

Results

Between 23-Sep-2020 and 16-Sep-2022, we randomly allocated 690 patients (n=345 each to BP02 and RT). In the ITT population, similar proportion of patients achieved ORR with BP02 (n=231, 67.0%, 95% CI 62.0, 71.9) and RT (n=238, 69.0%, 95% CI 64.1, 73.9). 95% CI of risk difference (-2.03, 95% CI -9.15, 5.09) was within the equivalence margins of ±13%. 90% CI of risk ratio (0.97, 90% CI 0.89, 1.06) was within the equivalence margins of (0.80, 1.25). TEAEs were seen in 58% and 60.3% patients; TEAEs leading to treatment withdrawal were reported in 2.9% and 3.2% patients, with BP02 and RT respectively.

Conclusions

BP02 showed equivalent efficacy and similar safety profile to RT.

Clinical trial identification

CTRI/2020/04/024456.

Editorial acknowledgement

Dr Vallish BN from MarksMan Healthcare Communications, India provided editorial assistance in writing of the abstract.

Legal entity responsible for the study

Curateq Biologics Private Limited, Hyderabad, India.

Funding

Curateq Biologics Private Limited, Hyderabad, India.

Disclosure

A. Prajapati, D. Dadke: Financial Interests, Personal, Full or part-time Employment: Curateq biologics. R.K. Kothari: Financial Interests, Personal, Financially compensated role: Zydus Pharmaceuticals, AstraZeneca, Glenmark, Novartis, Emcure, Fresenius Kabi, Bard Peripheral Vascular, Pfizer, Alkem Laboratories, Roche; Financial Interests, Institutional, Financially compensated role: Cipla, Merck, Celon Pharma, Bristol Myers Squibb Foundation; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Institutional, Research Funding: Zydus Pharmaceuticals, Lambda Therapeutic Research, Axis Clinicals, Reliance Life Sciences. All other authors have declared no conflicts of interest.