Preliminary efficacy and safety of TQB2102 in patients with HER2 low-expressing recurrent/metastatic breast cancer: Results from a phase 1b study.

Abstract

1090 Background: TQB2102 is a novel antibody-drug conjugate (ADC) comprised of a recombinant humanized anti-HER2 bispecific antibody that simultaneously binds to two distinct HER2 epitopes (ECD4 and ECD2), an enzyme-cleavable linker, and a DNA topoisomerase I inhibitor payload. This study aims to evaluate the efficacy and safety of TQB2102 for patients (pts) with HER2-expressing relapsed/metastatic breast cancer. Methods: This 1b phase, open-label, multicenter, randomized trial was divided into two cohorts: Pts in cohort 1 were HER2 low-expressing breast cancer and in cohort 2 were HER2 positive BC, all pts were refractory or intolerant to standard therapy. In cohort 1, HER2 low-expressing pts were randomly assigned to receive TQB2102 monotherapy at a dose of 6.0 mg/kg (Q3W, IV) or 7.5 mg/kg (Q3W, IV). The primary endpoint was ORR per RECIST v1.1, and the secondary endpoints were PFS, DCR and safety etc. Results: 73 HER2 low-expressing female pts were randomized to receive at least one dose of TQB2102 6mg/kg (n = 37) or 7.5mg/kg (n = 36), the median age was 53. All pts had received chemotherapy in the metastatic setting, and hormone receptor positive pts (n = 50) also had received prior CDK4/6 inhibitors. In cohort 1, pts had undergone a median of 4 prior treatment lines (range: 1-10) in the metastatic setting, the median prior lines of chemotherapy therapies were 2 (range: 1-5), and 12.3% (n = 9) pts had received prior ADCs. As of data cutoff on Nov 1, 2024, median follow-up time was 7.16 months. ORR was 53.4% (39/73) in cohort 1, and the ORR of 7.5mg/kg (58.3%) was better relative to 6.0mg/kg (48.7%). Objective responses were observed in subgroups with HR positive pts (27/50, ORR 54.0%), HR negative pts (12/23, ORR 52.2%); of which the ORR of 7.5mg/kg with HR+ and HR- was 66.7% (14/21) and 46.7% (7/15), respectively. For HER2 low-expressing pts who received prior ADC therapies, the ORR was 44.4% (4/9). In cohort 1, DCR was 86.3% (63/73, among 6 pts was not available), and median PFS was not yet mature. TRAEs were reported in 71 (97.3%) HER2 low-expressing pts. Grade≥3 TRAEs and serious TRAEs were reported in 30 (41.1%), 13 (17.8%) pts, respectively. The main TRAEs were neutropenia, leukopenia, anemia, nausea, vomiting. The common TRAEs and grade ≥3 TRAEs occurred similarly at both doses, with hematologic toxicities such as anemia were slightly higher at 7.5mg/kg than at 6.0mgkg, but all were tolerable. No Interstitial lung disease was reported in cohort 1 pts. Conclusions: TQB2102 was well-tolerated and showed promising antitumor activity in heavily pretreated HER2 low-expressing recurrent/metastatic breast cancer pts. The recommended phase 3 dose of TQB2102 in HER2 low-expressing r/m BC was 7.5 mg/kg Q3W. A phase III trial to evaluate the efficacy and safety of TQB2102 versus investigator-selected chemotherapy in HER2 low-expressing r/m BC is currently ongoing (NCT06561607). Clinical trial information: NCT06115902 .