firtecan pegol (PEG-SN38)

P2, N=43, Recruiting, Mayo Clinic | Trial primary completion date: Feb 2024 --> Feb 2025

P2, N=43, Recruiting, Mayo Clinic | Suspended --> Recruiting

P2, N=43, Suspended, Mayo Clinic | N=31 --> 43

The bonding of Fc-III-4C peptide with PLG-graft-mPEG/SN38 (Fc-NPLG-SN38) was achieved using a click reaction between azide and DBCO groups...aPDL1-NPLG-SN38 exhibited excellent therapeutic properties in both medium-sized and large MC38 tumor animal models. The present study provides the details of a novel preparation strategy for SN38-loaded ADCs having a high DAR.

P2, N=31, Suspended, Mayo Clinic | Active, not recruiting --> Suspended

P1/2, N=65, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting | N=10 --> 65

P2, N=160, Terminated, Enzon Pharmaceuticals, Inc. | Active, not recruiting --> Terminated; Program suspended and divested

P1/2, N=10, Suspended, National Cancer Institute (NCI) | N=65 --> 10 | Recruiting --> Suspended

P1/2, N=62, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2023

This study demonstrates the feasibility of using a single-mouse design for assessing the antitumor activity of an agent, while encompassing greater genetic diversity representative of childhood cancers. PLX038A was highly active in most xenograft models, and tumor sensitivity to PLX038A was correlated with sensitivity to irinotecan, validating the single-mouse design in identifying agents with the same mechanism of action. Biomarkers that correlated with model sensitivity included wild-type TP53, or mutant TP53 but with a mutation in 53BP1, thus a defect in DNA damage response. These results support the value of the single-mouse experimental design.

Here, we tested the hypothesis that a pharmacological compound previously shown to inhibit HIF-1α may act as a chemosensitizer by interrupting protective microenvironmental interactions and exposing CLL cells to fludarabine-induced cytotoxicity. We found that the camptothecin-11 analogue EZN-2208 sensitizes CLL cells to fludarabine-induced apoptosis in cytoprotective in vitro cultures; in vivo EZN-2208 improves fludarabine responses, especially in early phases of leukaemia expansion, and exerts significant anti-leukaemia activity, thus suggesting that this or similar compounds may be considered as effective CLL therapeutic approaches.