A B7H3-targeting antibody-drug conjugate in advanced solid tumors: a phase 1/1b trial.

Antibody-drug conjugates (ADCs) have emerged as a transformative modality in the treatment of solid tumors. YL201, a novel B7H3-targeting ADC, leverages a tumor microenvironment activable linker-payload platform, coupled with a novel topoisomerase 1 inhibitor via a protease-cleavable linker. Here we report the findings from a large-scale, global, multicenter, phase 1 trial evaluating the safety, pharmacokinetics and preliminary efficacy of YL201 in patients with advanced solid tumors refractory to standard therapies.

Anti-resonance in developmental signaling regulates cell fate decisions.

Cells process dynamic signaling inputs to regulate fate decisions during development. While oscillations or waves in key developmental pathways, such as Wnt, have been widely observed, the principles governing how cells decode these signals remain unclear. By leveraging optogenetic control of the Wnt signaling pathway in both HEK293T cells and H9 human embryonic stem cells, we systematically map the relationship between signal frequency and downstream pathway activation.

Phase 1 trial of durvalumab (anti-PD-L1) combined with lenalidomide in relapsed/refractory cutaneous T cell lymphoma.

Selective targeting of the functionally exhausted malignant T cells in cutaneous T-cell lymphoma (CTCL) and distinct cells within the tumor microenvironment (TME) via PD1/PD-L1 blockade (durvalumab) may restore an anti-tumor immune response. The oral immunomodulator lenalidomide, which has activity in CTCL, may enhance durvalumab immune checkpoint blockade. Our phase 1/2 clinical trial of durvalumab and lenalidomide in patients with refractory/advanced CTCL (NCT03011814) sought to assess safety and tolerability and identify the maximum tolerated dose/recommended phase 2 dose (RP2D) of lenalidomide plus fixed-dose durvalumab.

Integrated multi-month dispensing for HIV and hypertension in South Africa: A model of epidemiological impact and cost-effectiveness.

Introduction: In the current era of universal antiretroviral treatment (ART), health systems have the dual challenge of a growing number of people living with HIV and on ART who are also receiving chronic, life-long treatment for non-communicable diseases. Current evidence suggests that 6-month multi-month dispensing (6MMD) can maintain at least equivalent clinical outcomes to conventional care and reduce costs, but little is known when integrating 6MMD for multiple conditions. We examined the cost-effectiveness of integrated multi-month drug dispensing for people living with HIV and hypertension.