LBA15 - Primary outcome of the phase III SYD985.002/TULIP trial comparing [vic-]trastuzumab duocarmazine to physician’s choice treatment in patients with pre-treated HER2-positive locally advanced or metastatic breast cancer

Background

[vic-]Trastuzumab duocarmazine (SYD985, Byondis B.V., NL) is a novel HER2-targeting antibody–drug conjugate comprised of trastuzumab bound to a linker drug containing duocarmycin. TULIP assessed the efficacy of SYD985 in advanced HER2-positive breast cancer.

Methods

The TULIP trial (NCT03262935) randomly assigned HER2-positive locally advanced or metastatic breast cancer (MBC) patients with ≥ 2 previous MBC regimens or previous MBC treatment with T-DM1, 2:1 between SYD985 (1.2 mg/kg q three weeks) and physician’s choice (PC) chemotherapy. The primary endpoint was progression-free survival (PFS) by blinded central review. The trial was powered to detect a Hazard Ratio (HR) of 0.65 at the P < 0.05 significance level. Secondary endpoints were investigator-assessed PFS, overall survival (OS), objective response rate (ORR), and health-related quality of life (HRQoL).

Results

437 patients from 11 countries were randomized to SYD985 (n=291) or PC (n=146). Median age was 56 years, median number of prior MBC treatments was 4 [range 1-16]. Centrally reviewed median PFS was 7.0 months [95% CI 5.4-7.2] for SYD985 and 4.9 mo [4.0-5.5] for PC (HR 0.64 [0.49-0.84]; p = 0.002). Investigator-assessed PFS was also significantly improved (6.9 mo [6.0-7.2] vs 4.6 mo [4.0-5.6]; HR 0.60 [0.47-0.77]; p < 0.001). In this first analysis of OS the HR was 0.83 [0.62-1.09]; p = 0.153. No significant differences were observed in ORR or HRQoL. The most frequently reported adverse events for SYD985 were conjunctivitis (38.2%), keratitis (38.2%) and fatigue (33.3%), for PC these were diarrhoea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease / pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with SYD985, including two grade 5 events. Adverse events leading to discontinuation (SYD985 35.4%, PC 10.2%) in the SYD985 group were mainly related to eye disorders (20.8%) or respiratory disorders (6.3%).

Conclusions

Treatment with SYD985 significantly improved PFS in comparison with standard PC and may provide a new treatment option for patients with pre-treated locally advanced or metastatic HER2-positive MBC.

Clinical trial identification

NCT03262935.

Editorial acknowledgement

Legal entity responsible for the study

Byondis B.V., Nijmegen, The Netherlands.

Funding

Byondis B.V.

Disclosure

C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Exeter Pharma; Financial Interests, Personal, Advisory Board: F. Hoffmann - La Roche Ltd; Financial Interests, Personal, Advisory Board: MediTech; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Philips; Financial Interests, Personal, Advisory Board: Piere Fabre; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Roche Farma; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Advisory Board: SeaGen; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Personal, Other, SC: Byondis B.V.; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Eli Lilly and Company; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: Merck, Sharp and Dhome España S.A.; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Piqur Therapeutics; Financial Interests, Institutional, Research Grant: Puma; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Synthon; Financial Interests, Institutional, Research Grant: Zenith Pharma; Financial Interests, Institutional, Invited Speaker: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM); Non-Financial Interests, Member: American Society for Clinical Oncology (ASCO); Non-Financial Interests, Member: SOLTI group (Academic research group in breast cancer); Non-Financial Interests, Member: Geicam (Spanish Breast Cancer Research Group); Non-Financial Interests, Member: American Association for Cancer Research (AACR). J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie Inc; Financial Interests, Personal, Advisory Board: Agendia; Financial Interests, Personal, Advisory Board: Aptitude Health; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Celgene Corporation; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Gilead Sciences; Financial Interests, Personal, Advisory Board: GRAIL; Financial Interests, Personal, Advisory Board: Halozyme Therapeutics; Financial Interests, Personal, Advisory Board: Heron Therapeutics; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Ipsen Biopharmaceuticals; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Myriad; Financial Interests, Personal, Advisory Board: Nektar Therapeutics; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Ontada; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Pharmacyclics; Financial Interests, Personal, Advisory Board: Pierre Fabre Pharmaceuticals; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Personal, Advisory Board: Prime Oncology; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Samsung Bioepis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Syndax Pharmaceuticals; Financial Interests, Personal, Advisory Board: Taiho Oncology; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Synthon B.V.; Financial Interests, Personal, Advisory Board: Byondis B.V. P.G. Aftimos: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Macrogenics; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Amcure; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Radius; Financial Interests, Personal, Advisory Board: Deloitte; Financial Interests, Personal, Advisory Board: Menarini; Financial Interests, Personal, Advisory Board: Synthon; Financial Interests, Personal, Advisory Board: Byondis; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Role: Gilead; Non-Financial Interests, Personal, Other, Travel grant: MSD; Non-Financial Interests, Personal, Other, Travel grant: Pfizer; Financial Interests, Institutional, Funding: Roche; Financial Interests, Personal, Advisory Board: Sanofi-Aventis; Non-Financial Interests, Personal, Other, Travel grant: Roche; Non-Financial Interests, Personal, Other, Travel grant: Amgen; Non-Financial Interests, Personal, Other, Member of the scientific committee: IBCSG. E. van den Tweel: Financial Interests, Personal, Full or part-time Employment: Byondis B.V.; Non-Financial Interests, Personal, Member: ESMO; Non-Financial Interests, Personal, Member: ASCO. M. Oesterholt: Financial Interests, Personal, Full or part-time Employment: Byondis B.V. S.I. Escrivá-de-Romaní: Financial Interests, Personal, Invited Speaker, Advisory board, Travel grants: Roche; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Advisory Board, Invited speaker, travel grants: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Invited speaker, travel grant: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Research Grant: Zymeworks; Financial Interests, Institutional, Research Grant: Synthon B.V.; Financial Interests, Institutional, Research Grant: Byondis B.V.; Financial Interests, Personal, Advisory Board: Seagen. N. Quenel Tueux: Financial Interests, Institutional, Principal Investigator: Byondis B.V. T.J. Tan: Financial Interests, Personal and Institutional, Advisory Board, Invited speaker, Board & Principal Investigator: Novartis; Financial Interests, Personal and Institutional, Advisory Board, Principal Investigator: Roche; Financial Interests, Personal, Speaker’s Bureau, Advisory board: DKSH; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker, Advisory board: MSD; Financial Interests, Personal and Institutional, Invited Speaker, Advisory board, Principal Investigator, Research grant: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: Seagen. J.S. Lim: Financial Interests, Personal, Invited Speaker, Advisory board: AstraZeneca; Financial Interests, Personal, Advisory Board, Invited speaker: DKSH; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Institutional, Funding: CTI Biopharma; Non-Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Non-Financial Interests, Institutional, Principal Investigator: Byondis B.V.; Non-Financial Interests, Institutional, Principal Investigator: Synthon B.V.; Non-Financial Interests, Institutional, Principal Investigator: Taiho Pharmaceuticals. S. Ladoire: Financial Interests, Institutional, Principal Investigator: Byondis B.V. A. Armstrong: Financial Interests, Institutional, Principal Investigator: Byondis B.V. T. Crook: Financial Interests, Institutional, Principal Investigator: Byondis B.V.; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Daiichi Sankyo. A. Stradella: Financial Interests, Institutional, Principal Investigator: Byondis B.V.; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal and Institutional, Expert Testimony: Seagen. G. Bianchi: Financial Interests, Institutional, Principal Investigator: Byondis B.V.; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche. R. Mulder: Financial Interests, Personal, Full or part-time Employment: Byondis B.V. N. Koper: Financial Interests, Personal, Full or part-time Employment: Byondis B.V. N. Turner: Financial Interests, Institutional, Principal Investigator: Byondis B.V.; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck Sharpe and Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche/Genentech; Financial Interests, Personal, Advisory Board: Bicycle Therapeutics; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Advisory Board: Zeno Phamraceuticals; Financial Interests, Personal, Advisory Board: Repare therapeutics; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: BioRad; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Roche/Genentech; Financial Interests, Institutional, Funding: Clovis; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Guardant Health; Non-Financial Interests, Personal, Advisory Board: Byondis B.V.