HR+ Breast Cancer

The goal of this open-label dose escalation and expansion study is to evaluate the safety and tolerability of NKT5097 in adults with advanced/metastatic tumors (emphasis on breast cancer and solid tumors with CCNE1 amplification). Main questions to answer include: * What is the recommended dose for expansion and/or Phase 2, for both monotherapy and in combination with ET * What medical issues/symptoms do participants experience when taking NKT5097 as monotherapy as well as in combination with ET

Breast cancer is the most common malignancy in women, with approximately 20% classified as HER2-positive. Anti-HER2 blockade (trastuzumab plus pertuzumab) combined with chemotherapy constitutes the standard neoadjuvant regimen; however, the pathological complete response (pCR) rate in the HR-positive subgroup remains only 35-40%, and platinum-containing schedules are associated with significant hematologic toxicity. Antibody-drug conjugates (ADCs) integrate targeted delivery with potent cytotoxic payloads. SHR-A1811 (ruikang-trastuzumab), a domestically developed ADC by Hengrui Pharmaceutical, is conjugated with a topoisomerase I inhibitor (mean drug-to-antibody ratio \[DAR\] ≈ 6). Preclinical data demonstrate that SHR-A1811 exhibits superior efficacy to trastuzumab emtansine (T-DM1) in both trastuzumab-sensitive and resistant HER2-expressing tumor models, with a manageable safety profile. This prospective, open-label, phase II trial will enroll patients with early-stage/locally advanced HR-positive/HER2-positive breast cancer, who will receive neoadjuvant SHR-A1811 plus pertuzumab. At baseline, BluePrint gene profiling will be performed to stratify participants into luminal and non-luminal subtypes: patients with luminal subtype who achieve stable disease (SD) after 4 cycles will switch to a regimen of trastuzumab, pyrotinib, dalpiciclib, and an aromatase inhibitor for an additional 4 cycles; all other patients will continue ADC-based dual-target therapy for 2-4 further cycles, followed by surgical resection. Circulating tumor DNA (ctDNA) dynamics will be dynamically monitored at baseline, after 4 cycles of treatment, and preoperatively to evaluate early treatment sensitivity. The primary endpoint is the pCR rate. Secondary endpoints include event-free survival (EFS), objective response rate (ORR), and safety profiles. Exploratory analyses will investigate the correlation between molecular subtypes and treatment responses, aiming to establish a chemotherapy-free, precision neoadjuvant strategy for HR-positive/HER2-positive breast cancer.

Phase III, single-center, randomized, double-blind, placebo-controlled, 2x2 cross- over study, assessing the efficacy of CBD in patients with early HR+ BC, presenting aromatase inhibitor-related musculoskeletal pain

This study is an open-label, multicenter Phase IIa trial to evaluate the efficacy and safety of SC-101 monotherapy in patients with locally advanced or metastatic malignant tumors who are positive for NECTIN4 gene amplification.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors combined with hormonal therapy are the current standard frontline treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER-2)-negative metastatic breast cancer (MBC). However, the optimal treatment after progression on CDK4/6 inhibitors remains unknown. Anlotinib is an oral multi-target tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. This study aimed to evaluate the safety and efficacy of anlotinib-based combination therapy in patients with HR+ MBC previously treated with a CDK4/6 inhibitor.