P2, N=702, Recruiting, West German Study Group | Active, not recruiting --> Recruiting | N=402 --> 702 | Trial completion date: Jun 2029 --> Sep 2030 | Trial primary completion date: Jun 2025 --> Jun 2030

Our findings revealed that statin use significantly enhanced the efficacy of T-DXd in both a preclinical HER2-negative rat model and patients with HER2-positive mBC. Prospective clinical trials are warranted to validate these observations.

The agonist combines cRGD peptide-targeted polydopamine-coated zeolitic imidazolate framework-8 with the photosensitizer indocyanine green and the chemotherapeutic drug topotecan...The mild photothermal therapy-induced immunogenic cell death promotes the initiation of antitumor immunity, while also enhancing the effectiveness of immune checkpoint blockade. In vivo studies show that cDZ@IP significantly inhibits primary and distant tumor growth and prevents lung metastasis, providing a promising strategy for STING pathway-targeted cancer immunotherapy.

In these studies, trastuzumab deruxtecan, a HER2-targeted ADC, demonstrated notable intracranial responses in patients with active CNS disease, suggesting that CNS barriers are dynamically remodeled within the tumor microenvironment to permit drug access...By integrating emerging clinical evidence with key pharmacological determinants and tumor-associated microenvironmental changes, this review delineates the mechanisms governing ADC activity in brain metastases and identifies critical factors underlying intracranial response. Collectively, these insights provide a mechanistic framework to guide the rational design of next-generation ADCs and optimize therapeutic strategies for patients with advanced CNS involvement.

P2, N=132, Not yet recruiting, Akeso

P2/3, N=900, Recruiting, AbbVie | Not yet recruiting --> Recruiting

DS-8201 demonstrates potential as one of the effective salvage therapies following RC48 failure in HER2 altered solid tumors, showing significantly better disease control and a distinct, manageable toxicity profile. These findings highlight the importance of selecting personalized ADCs based on molecular subtypes and toxicity factors and provide a basis for future, larger-scale prospective studies.

P2, N=60, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

P3, N=700, Not yet recruiting, Qilu Pharmaceutical Co., Ltd.

Durvalumab plus T-DXd demonstrated clinically relevant efficacy for first-line treatment of metastatic HR-negative, HER2-low breast cancer, with no unexpected toxicities observed. ClinicalTrials.gov identifier: NCT03742102 .

Using a Sonic Hedgehog (SHH)-driven mouse model, two patient-derived xenografts (SHH and group 3), and drug-resistant TP53-mutant MB cells, we found that T3 and cytotoxic chemotherapy suppress tumor growth through complementary biological mechanisms: T3 promotes terminal differentiation of tumor cells, whereas cyclophosphamide (CTX) and irinotecan (CPT-11) induce caspase-3-dependent apoptosis. T3-induced transient tachycardia was effectively controlled with propranolol without compromising antitumor activity. Together, these findings support the potential of T3 as a clinically accessible differentiation-based therapy that enhances chemotherapy responses and suppresses post-treatment tumor regrowth in medulloblastoma.

P2, N=277, Active, not recruiting, Daiichi Sankyo | Trial completion date: Jul 2026 --> Jan 2027