P1, N=26, Active, not recruiting, Peptomyc S.L. | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2025 --> May 2026

KLF4 serves as a hub gate orchestrating cell crosstalk within the TME. Understanding its context-dependent functions may facilitate the development of KLF4-targeted therapies for precision oncology.

P2 exhibited a ∼10-fold increase in antiproliferative potency against human leukemic cell lines compared to homoharringtonine (HHT)...Our findings provide valuable insights to guide the future structural optimization of harringtonine derivatives. Furthermore, P2 has been identified as a promising anti-leukemic candidate and warrants further development.

In this study, we propose a Gas-Metal Synergy Strategy, which integrates immune activation and biosafety, by engineering a pH-responsive manganese-based zeolitic imidazolate framework (named MRPH) nanoplatform co-loaded with the nitric oxide (NO) donor RRX-001...Both in vitro and in vivo studies demonstrate that MRPH significantly enhances gas-amplified metalloimmunotherapy. This work pioneers a low-toxicity paradigm that integrates gas therapy and metal-based immunotherapy, offering a transformative approach to solid tumor immunotherapy.

In vivo, the anti-leukemic efficacy of HHT was significantly diminished upon EWSR1 knockdown, demonstrating that EWSR1 was required for therapeutic response. Collectively, these findings uncover a phase separation-centric mechanism by which HHT exerts anti-AML activity, establish the EWSR1-YTHDF2-m6A axis as a critical regulator of leukemia progression, and position EWSR1 as both a functional target and a predictive biomarker for optimizing HHT-based therapies.

This study highlights the value of computational drug repurposing platforms for accelerating therapeutic discovery. Further preclinical investigations are warranted to evaluate HHT's in vivo efficacy and clinical applicability in RPF.

Our study demonstrates the utility of cancer organoids in drug discovery and identifies HHT as a promising therapeuticagent for ATC.

P1/2, N=28, Active, not recruiting, University of Colorado, Denver | Trial primary completion date: Aug 2026 --> Oct 2025

Infiltrative mediastinal/retroperitoneal MS may present with esophageal obstruction and mimic lymphoma or carcinoma. High-index suspicion, targeted biopsy with high-power morphology, and a focused immunohistochemical panel are critical for timely diagnosis and treatment initiation.

Here we show that the BET inhibitor PLX51107 potently suppresses the growth of NRAS -mutant AML cell lines, and that these activities are enhanced by co-treatment with the MEK inhibitor PD0325901. AMLs that relapsed after frontline chemotherapy showed similar transcriptional remodeling. These studies demonstrate transcriptional plasticity in primary AMLs that relapse following in vivo treatment with either targeted agents or chemotherapy, and support evaluating BET inhibition in leukemias with monocytic differentiation and RAS mutations.

Treatment with the MYC(N)/MAX dimerization inhibitor MYCi975 reduced ALCAM expression by immunoblotting and luciferase signal from the ALCAM promoter. Finally, as ALCAM is expressed in several normal tissues, we investigated an ALCAM-targeted conditionally activated antibody drug conjugate (ADC), CX-2009 (praluzatamab ravtansine), which delayed tumor growth in two out of three PDX models. Together, these findings credential ALCAM as an immunotherapeutic target in neuroblastoma.

P1/2, N=24, Terminated, M.D. Anderson Cancer Center | Completed --> Terminated; The study terminated early because the company was longer providing the investigational product.