A signal-seeking phase 2 study of Trastuzumab emtansine in tumours harbouring HER2 amplification or mutation

Subotheni Thavaneswaran; Frank Lin; John P Grady; David Espinoza; Min Li Huang; Sarah Chinchen; Lucille Sebastian; Maya Kansara; Tony Mersiades; Chee Khoon Lee; Jayesh Desai; Peter Grimison; Michael Brown; Michael Millward; Rosemary Harrup; Ken O'Byrne; Adnan Nagrial; Paul Craft; John Simes; Anthony M Joshua; David M Thomas

doi:10.1038/s41698-024-00698-4

A signal-seeking phase 2 study of Trastuzumab emtansine in tumours harbouring HER2 amplification or mutation

NPJ Precis Oncol. 2024 Sep 9;8(1):195. doi: 10.1038/s41698-024-00698-4.

Authors

Subotheni Thavaneswaran^{1

2

3

4}, Frank Lin^{5

6

7

8}, John P Grady⁷, David Espinoza⁵, Min Li Huang^{6

9}, Sarah Chinchen⁵, Lucille Sebastian⁵, Maya Kansara⁷, Tony Mersiades⁵, Chee Khoon Lee⁵, Jayesh Desai¹⁰, Peter Grimison¹¹, Michael Brown¹², Michael Millward¹³, Rosemary Harrup¹⁴, Ken O'Byrne¹⁵, Adnan Nagrial¹⁶, Paul Craft¹⁷, John Simes⁵, Anthony M Joshua^{18

6

7}, David M Thomas^{18

7

19}

Affiliations

¹ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia. [email protected].
² The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW, Australia. [email protected].
³ School of Clinical Medicine, Faculty of Medicine and Health, University of NSW, Sydney, NSW, Australia. [email protected].
⁴ Garvan Institute of Medical Research, Sydney, NSW, Australia. [email protected].
⁵ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
⁶ School of Clinical Medicine, Faculty of Medicine and Health, University of NSW, Sydney, NSW, Australia.
⁷ Garvan Institute of Medical Research, Sydney, NSW, Australia.
⁸ Kinghorn Centre for Clinical Genomics, Sydney, NSW, Australia.
⁹ SydPath Department of Anatomical Pathology, St Vincent's Hospital, Sydney, NSW, Australia.
¹⁰ Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
¹¹ Chris O'Brien Lifehouse, Sydney, NSW, Australia.
¹² Royal Adelaide Hospital, Adelaide, SA, Australia.
¹³ Linear Clinical Research & University of Western Australia, Perth, WA, Australia.
¹⁴ Royal Hobart Hospital, Hobart, TAS, Australia.
¹⁵ Princess Alexandra Hospital and Queensland University of Technology, Brisbane, QLD, Australia.
¹⁶ Westmead Hospital, Sydney, NSW, Australia.
¹⁷ The Canberra Hospital, Canberra, ACT, Australia.
¹⁸ The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW, Australia.
¹⁹ Centre for Molecular Oncology, University of New South Wales, Sydney, NSW, Australia.

Abstract

This single-arm phase II non-randomised trial (ACTRN12619001265167) evaluated trastuzumab emtansine in solid cancers with HER2 amplification or mutation detected by comprehensive genomic profiling. The primary objective was objective response (OR), while secondary objectives included the time to progression (TTP) on study to TTP on prior therapy ratio, progression-free survival (PFS) and overall survival (OS). The cohort included 16 tumours with HER2 mutations (group 1) and 16 with HER2 amplification (group 2). After 17 months median follow-up, ORs occurred in 19% of group 1 (1 salivary gland carcinoma (SGC), 2 lung cancers) and 25% of group 2 (3 SGCs, 1 uterine carcinoma). Fourteen of 29 TTP-evaluable patients achieved a TTP ratio ≥1.3, including 10 without an OR. Median PFS and OS were 4.5 (95% CI 2.1-7.0) and 18.2 months (95% CI 8.1-not reached) respectively. Trastuzumab emtansine showed modest ORs and a favourable change in disease trajectory in select HER2-altered solid cancers.