sulanemadlin (ALRN-6924)

P1, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2025 --> Jul 2027 | Trial primary completion date: Jul 2025 --> Jul 2027

We demonstrated that a mtp53-MDM2/MDMX complex promoted 53BP1-MDC1 interactions by showing that mtp53-MDM2/MDMX complex disruptors, Nutlin 3a and ALRN-6924, reduced the 53BP1-MDC1 nuclear interactions (especially in S-phase)...We found that MDM2-deficient cells have increased poly-ADP-ribosylation on chromatin which supports the possibility that a mtp53-MDM2/MDMX pathway promotes aberrant DNA repair. Taken together, our data suggest that a mtp53-MDM2/MDMX complex orchestrates DNA repair machinery activity on chromatin, thus priming cancer cells for persistent DNA damage repair (CPR).

P1, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Phase classification: P1b --> P1

P1b, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2023 --> Apr 2025 | Trial primary completion date: Jul 2023 --> Apr 2025

P1, N=21, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | N=69 --> 21

While some MDM2 inhibitors have progressed to early phase clinical trials in GBM, their efficacy, alone and in combination, is yet to be confirmed. In this article, we present an overview of MDM2 inhibitors currently under preclinical and clinical investigation, with a specific focus on the drugs being assessed in ongoing clinical trials for GBM patients.

A recent report describes that ALRN-6924, an ATSP-7041 analog, inhibited OATP activities in vivo; therefore, we focused on the interaction between ATSP-7041 and OATP1B1 to demonstrate that ATSP-7041, as a higher molecular weight stapled peptide, is a substrate and strong inhibitor of OATP1B1 activity. Our findings demonstrated the possibility of transporter-mediated DDI potential by high molecular weight stapled peptides and the necessity of their evaluation for drug development.

P1, N=69, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2023 --> Sep 2023 | Trial primary completion date: Jun 2023 --> Sep 2023

P1, N=69, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting

P1b, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Two new drugs, Trilaciclib and ALRN-6924 may cause a temporary cell cycle arrest (CCA) of normal cells without blocking the proliferation of the neoplastic ones and render the normal cells temporarily invulnerable to the toxicity of chemotherapy. It may allow the treatment of frail patients with full chemotherapy doses. It is also reasonable to expect that may complications other common and sometimes lethal complications of chemotherapy such as stomatitis, esophagitis, diarrhea and dehydration.

P1b, N=6, Terminated, Aileron Therapeutics, Inc. | N=26 --> 6 | Trial completion date: Jan 2024 --> Feb 2023 | Recruiting --> Terminated | Trial primary completion date: Sep 2023 --> Feb 2023; The study has been terminated early given that the first four patients enrolled have experienced Grade 4 neutropenia and alopecia after cycle 1 and as such failed to meet the primary endpoint and the main secondary endpoint.