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

Area of Science:

• Oncology
• Genomics
• Pharmacology

Background:

• Solid tumors with HER2 amplification or mutation represent a targetable subset.
• Comprehensive genomic profiling (CGP) is crucial for identifying these alterations.
• Trastuzumab emtansine is an antibody-drug conjugate with potential activity in HER2-altered cancers.

Purpose of the Study:

• To evaluate the efficacy of trastuzumab emtansine in solid cancers with HER2 amplification or mutation.
• To determine objective response (OR) rates as the primary endpoint.
• To assess secondary endpoints including time to progression (TTP) ratio, progression-free survival (PFS), and overall survival (OS).

Main Methods:

• Single-arm, phase II, non-randomised trial (ACTRN12619001265167).
• Patients with solid cancers and detected HER2 alterations via CGP were enrolled.
• Two cohorts were defined: 16 patients with HER2 mutations and 16 with HER2 amplification.

Main Results:

• Objective response rates (ORs) were 19% in the HER2 mutation cohort and 25% in the HER2 amplification cohort.
• Notable responses included salivary gland carcinoma and lung cancer (mutation group), and salivary gland carcinoma and uterine carcinoma (amplification group).
• Fourteen of 29 TTP-evaluable patients achieved a TTP ratio ≥1.3, with 10 not achieving an OR.

Conclusions:

• Trastuzumab emtansine exhibited modest objective responses in select HER2-altered solid cancers.
• The drug demonstrated a favorable change in disease trajectory, indicated by TTP ratios.
• This suggests a potential role for trastuzumab emtansine in specific patient populations identified by genomic profiling.