TQB2102 Generates Antitumor Activity in Pretreated HER2-Low Breast Cancer

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Treatment with the novel, bispecific antibody-drug conjugate (ADC) TQB2102 produced responses and was well tolerated in patients with pretreated, recurrent or metastatic, HER2-positive breast cancer, according to data from a phase 1b trial (NCT06115902).

Findings presented at the 2025 ASCO Annual Meeting showed that patients in the HER2-low cohort (n = 73) achieved an overall response rate (ORR) of 53.42%, comprising a complete response (CR) rate of 1.73% and a partial response (PR) rate of 52.05%. The stable disease and progressive disease rates were 32.88% and 5.48%, respectively. Notably, 8.22% of patients were not evaluated for response. The disease control rate (DCR) was 86.30%.

Regarding safety, most treatment-related adverse effects (TRAEs) were hematological and gastrointestinal in nature. The rates of any-grade and grade 3 or higher TRAEs were similar between the 2 dose levels, and no instances of interstitial lung disease occurred.

“The phase 3 dose of TQB2102 in HER2 low–expressing recurrent/metastatic breast cancer was [established at] 7.5 mg/kg once every 3 weeks,” lead study author Shusen Wang, MD, of the Department of Medical Oncology at Sun Yat-Sen University Cancer Center in Guangzhou, China, and colleagues wrote in a poster presentation. “A phase 3 trial [NCT06561607] to evaluate the efficacy and safety of TQB2102 vs investigator-selected chemotherapy in HER2 low–expressing recurrent/metastatic breast cancer is currently ongoing.”

Diving into the Study of TQB2102

The bispecific ADC targets both the ECD2 and ECD4 epitopes in the HER2 extracellular domain, and it is attached to a topoisomerase I inhibitor by an enzyme-cleavable linker.

In the open-label, multicenter, randomized, phase 1b study, investigators enrolled patients with HER2-low breast cancer (cohort 1) and HER2-positive breast cancer (cohort 2). In cohort 1, at least 1 prior line of chemotherapy was required, and those with hormone receptor (HR)–positive disease were required to be endocrine refractory with prior exposure to a CDK4/6 inhibitor.

Patients with HER2-low breast cancer were randomly assigned 1:1 to receive TQB2102 at 6.0 mg/kg or 7.5 mg/kg once every 3 weeks.

ORR served as the trial’s primary end point. Secondary end points consisted of DCR, duration of response (DOR), progression-free survival (PFS), and safety.

In the overall HER2-low cohort, the majority of patients were under 60 years of age (72.60%), had an ECOG performance status of 1 (78.08%), had immunohistochemistry (IHC) 1+ HER2 expression (67.12%), had HR-positive disease (68.49%), and had at least 3 metastatic sites (69.86%). Most patients had visceral metastases (86.30%), including liver metastases (63.01%) and lung metastases (46.58%).

Patients received a median of 4 prior lines of therapy (range, 1-10), and 50.68% received at least 4 lines. The median number of prior lines of chemotherapy was 2 (range, 1-5), and 57.53% received at least 2 lines.

Additional Efficacy and Safety Findings

At the 7.5-mg/kg dose, the ORR was 58.33%, comprised exclusively of PRs. At the 6.0-mg/kg dose, the ORR was 48.65%, which included 1 CR (2.70%) and a PR rate of 45.95%. The DCRs at the 7.5- and 6.0-mg/kg dose levels were 86.11% and 86.49%, respectively.

In patients with IHC 1+ HER2 expression, the ORR was 40.82%. This rate was 79.17% among patients with IHC 2+/in situ hybridization– HER2 expression. Patients who received a prior ADC experienced an ORR of 44.4%. In patients with HR-positive and HR-negative disease, the respective ORRs were 54.0% and 52.2%.

DOR and PFS data were not mature at the time of this analysis.

The most common TRAEs reported across the total cohort included neutropenia (any-grade, 76.71%; grade ≥3, 23.29%), decreased white blood cell count (73.97%; 20.55%), anemia (68.49%; 8.22%), nausea (68.49%; 0%), vomiting (54.79%; 4.11%), increased aspartate aminotransferase levels (49.32%; 2.74%), increased alanine aminotransferase levels (43.84%; 0%), diarrhea (41.10%; 0%), decreased appetite (41.10%; 1.37%), thrombocytopenia (39.73%; 5.48%), fatigue (35.62%; 4.11%), hypoalbuminemia (27.40%; 0%), hypokalemia (26.03%; 6.85%), decreased lymphocyte count (19.18%; 5.48%), and weight loss (19.18%; 0%).

Reference

Wang S, Zhang Q, Yang J, et al. Preliminary efficacy and safety of TQB2102 in patients with HER2 low-expressing recurrent/metastatic breast cancer: results from a phase 1b study. J Clin Oncol. 2025;43(suppl 16):1090. doi:10.1200/JCO.2025.43.16_suppl.1090