Efficacy and Safety of Neoadjuvant TQB2102 in Locally Advanced or Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: A Randomized, Open-Label, Multicenter, Phase II Trial

Author(s): Jun-Jie Li, MD, PhD^1,2,3; Wen-Juan Zhang, MD, PhD^1,2,3; Xiao-Hua Zeng, MD, PhD⁴; Qing-Yuan Zhang, MD, PhD⁵; Li Chen, MD, PhD^1,2,3; Jiong Wu, MD, PhD^1,2,3; Guang-Yu Liu, MD, PhD^1,2,3; Zhi-Hong Wang, BM⁶; Xiao-Bo Hu, MD⁷; Yan-Yan Hu, MD⁸; Zhen-Ling Li, MD⁸; Zhi-Ming Shao, MD, PhD^1,2,3;

Source: DOI: 10.1200/JCO-25-01153

Dr. Anjan Patel's Thoughts

The QUIWI study used quizartinib, a FLT3 drug added to standard chemo induction/consolidation in FLT-negative acute myeloid leukemia (AML) patients. There was a meaningful overall survival (OS) improvement across all age and risk groups including the NPM1+ population. They purposefully used a higher dose to achieve what is felt to be off-target TKI activity in familiar pathways of KIT, PDGRF…etc.

PURPOSE

To evaluate the efficacy and safety of the bispecific human epidermal growth factor receptor 2 (HER2)–directed antibody-drug conjugate (ADC) TQB2102 in the neoadjuvant treatment of HER2-positive breast cancer.

PATIENTS AND METHODS

This randomized, open-label, multicenter, phase II study (ClinicalTrials.gov identifier: NCT06198751) enrolled HER2-positive patients with stage II and III disease. Patients were stratified by hormone receptor status and randomly assigned (1:1) to receive 6.0 mg/kg once every 3 weeks of TQB2102 for six (cohort 1) or eight cycles (cohort 2) or 7.5 mg/kg once every 3 weeks for six (cohort 3) or eight cycles (cohort 4). The primary end point was total pathologic complete response (tpCR) rate across all four cohorts (n = 26 per cohort). When the lower limit of the 90% CI (Clopper-Pearson exact binomial test) for tpCR rate exceeded 40%, efficacy was considered better than that of the historical control.

RESULTS

Between February 5, 2024, and September 24, 2024, 104 patients were enrolled, with 26 patients in each cohort. The tpCR rates were 57.7% (15 of 26 [90% CI, 43.2 to 71.3]; P = .04) for cohort 1, 76.9% (20 of 26 [90% CI, 62.3 to 87.6]; P < .01) for cohort 2, 61.5% (16 of 26 [90% CI, 46.5 to 74.8]; P = .02) for cohort 3, and 69.2% (18 of 26 [90% CI, 54.6 to 81.3]; P < .01) for cohort 4. The incidence rates of grade ≥3 treatment-related adverse events were 23.1% (6 of 26) for cohort 1, 30.8% (8 of 26) for cohort 2, 30.8% (8 of 26) for cohort 3, and 26.9% (7 of 26) for cohort 4. No treatment-related deaths occurred in any groups.

CONCLUSION

To our knowledge, this was the first study to report the efficacy and safety of the bispecific HER2-directed ADC TQB2102 in the neoadjuvant setting for HER2-positive breast cancer. TQB2102 showed robust activity and was well-tolerated.

Author Affiliations

¹Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; ²Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; ³Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China; ⁴Breast Cancer Center, Chongqing Cancer Hospital, Chongqing, China; ⁵Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China; ⁶Thyroid and Breast Surgery, Guizhou Cancer Hospital, Guiyang, China; ⁷Breast Surgical Department 1, Hunan Cancer Hospital, Changsha, China; ⁸CHIA TAI Tianqing Pharmaceutical Group Co., Ltd, Jiangsu, China

Low-Dose Tamoxifen in Noninvasive Breast Neoplasia: Long-Term Results From an Individual-Participant Data Pooled Analysis

Among 1,545 women included with a median follow-up of 9.4 years in postmenopausal women, breast cancer events occurred in 40 of 335 receiving low-dose tamoxifen versus 93 of 401 controls HR, 0.51, with a 10-year absolute reduction of 11.2%. Among premenopausal women, no significant reduction was observed dose was 5mg daily of 10mg every other day in ductal carcinoma in situ (DCIS) and high-risk pts. Less is as good.

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HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer

Progression-free survival (PFS) was statistically significantly improved with addition of tucatinib versus placebo 24.9 v 16.3 months regardless of the presence/absence of BM or hormone receptor status.

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