Focus V (anlotinib)

The TMEp phase integrated stereotactic body radiotherapy (SBRT), low-dose etoposide, and anlotinib, followed by CI with the programmed death 1 (PD-1)/cytotoxic T lymphocyte antigen 4 (CTLA-4) bispecific antibody cadonilimab and concurrent probiotic supplementation...The TMEp-CI-M platform may enhance the efficacy of immunotherapy in ES-SCLC, enabling durable responses even in patients with brainstem metastases. Although this platform has demonstrated promise across multiple tumor types, further prospective and mechanistic studies are warranted to confirm its clinical utility.

This research pioneers the identification of anlotinib as an ER stress- and autophagy-dependent ICD inducer in HCC. Our comprehensive mechanistic dissection and robust preclinical evidence establish anlotinib's ability to convert immunologically "cold" tumors to "hot" ones through the FGFR-1/ER stress/autophagy/DAMP release axis. The synergy with anti-PD-1 and enhancement by metformin provide a rationale for novel combination strategies to overcome current limitations of targeted-immunotherapy, offering a promising approach to improve response rates in advanced HCC.

EV-derived miR-941 as a key driver of anlotinib resistance via the Keap1/Nrf2 pathway represent a promising non-invasive predictive biomarker and a potential therapeutic target for overcoming resistance in NSCLC.

P2, N=34, Recruiting, Qilu Hospital of Shandong University | Not yet recruiting --> Recruiting

Enrolled patients received 5 cycles of anlotinib (12 mg qd, d1‒14; q3w) plus 6 cycles of nab-paclitaxel (200 mg/m2, q3w), pirarubicin (50 mg/m2, q3w), and cyclophosphamide (500 mg/m2, q3w). Supporting evidence from an exploratory inverse probability of treatment weighting (IPTW) analysis using a real-world cohort receiving chemotherapy alone indicated a potential benefit of the combination over chemotherapy alone. In conclusion, neoadjuvant anlotinib plus chemotherapy demonstrates promising efficacy and manageable safety in HR+/HER2- breast cancer with a high Ki-67 index.

P2, N=49, Completed, Sun Yat-sen University | Recruiting --> Completed

P2, N=70, Completed, Sun Yat-sen University | Recruiting --> Completed | Trial completion date: May 2024 --> Dec 2025 | Trial primary completion date: Mar 2024 --> Oct 2025

Following eight cycles of ifosfamide plus epirubicin chemotherapy, tumor burden was reduced by more than 90%. Although first-line chemotherapy produced marked pulmonary tumor regression, subsequent anlotinib maintenance therapy did not prevent disease progression. In this PD-L1-positive tumor (CPS 10), sintilimab-based combination therapy yielded a marked clinical and radiographic response, supporting further investigation of ICI-based therapy in selected patients with metastatic MPT.

P2, N=152, Not yet recruiting, The Third Xiangya Hospital of Central South University

P2, N=31, Active, not recruiting, Xijing Hospital | Recruiting --> Active, not recruiting | Trial completion date: Jul 2025 --> Jul 2028

Subsequently, three cycles of systemic chemotherapy (albumin-bound paclitaxel combined with carboplatin) were tried, but they were discontinued because of extreme toxicity. This highlights the importance of life-long surveillance, including chest and crinial imagings. The partial remission with anlotinib underscores its value as a therapeutic option in this setting.

P2, N=26, Active, not recruiting, West China Hospital