Orally administered MOMA-341 as monotherapy or combination therapy in participants with advanced or metastatic solid tumors: Phase 1 study design
Date
2025
Authors
Lemech, C.
Humphries, T.
Biachi de Castria, T.
Cercek, A.
Overman, M.
Kummar, S.
Baldini, C.
Tabernero, J.
Hansen, A.
Nagrial, A.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Conference item
Citation
Molecular Cancer Therapeutics, 2025, vol.24, iss.Supl_10, pp.B003-1-B003-2
Statement of Responsibility
Charlotte Lemech, Timothy Humphries, Tiago Biachi de Castria, Andrea Cercek, Michael Overman, Shivaani Kummar, Capucine Baldini, Josep Tabernero, Aaron Hansen, Adnan Nagrial, Kate Roberts, Rohit Joshi, Elizabeth Ahern, Douglas Orr, Najeeb Al Hallak, Brian A. Van Tine, David Waller, Salah Nabhan, Allison Drew, Marc Ballas
Conference Name
International Conference on Molecular Targets and Cancer Therapeutics (22 Oct 2025 - 25 Oct 2025 : Boston, MA)
Abstract
Background: Patients with advanced or metastatic solid tumors harboring microsatellite instability high (MSI-H) or DNA mismatch repair deficiency (dMMR) alterations have benefited from immune check point inhibitors (ICIs). However, many patients show innate or acquired resistance to ICIs. Therefore, additional therapies with rapid response rates and longer durations of response are needed. Tumors with MSI-H or dMMR alterations rely heavily on DNA repair mechanisms to avoid apoptosis and may respond well to inhibition of Werner RecQ like helicase (WRN), a protein with a critical role in DNA replication and repair. WRN activity is required for successful DNA replication at expanded thymine and adenine (TA) dinucleotide repeats occurring from dMMR. Loss of WRN leads to DNA damage at TA repeat sites, resulting in cell death and tumor regression. MOMA-341 is a potent and selective oral inhibitor of WRN that has demonstrated antitumor activity in dMMR/MSI-H models. DNA damage and anti-tumor activity are enhanced when MOMA-341 is combined with standard chemotherapies (eg, irinotecan). The selective activity of MOMA-341 supports its development as monotherapy or combination therapy for treatment of dMMR/MSI-H solid tumors
School/Discipline
Dissertation Note
Provenance
Description
Abstract number B003