P1, N=570, Not yet recruiting, Sanofi

P2, N=72, Recruiting, Acrivon Therapeutics | N=48 --> 72

P1/2, N=48, Not yet recruiting, Acrivon Therapeutics Inc.

Co-treatment with interferon-γ further amplified PD-L1 and γH2A.X expression, highlighting a link between CHK1 inhibition, DNA damage, and immune checkpoint modulation. These findings suggest that Prexasertib not only enhances the cytotoxic effects of cisplatin but also influences immune signaling, providing a mechanistic rationale for future exploration of combined DNA damage response inhibition with immune checkpoint blockade.

Dual targeting of CHK1 and PD-L1 may improve OC treatment by simultaneously suppressing stemness and enhancing anti-tumor immunity.

FSTL3 overexpression completely abrogated tumor response to PPC treatment (Prexasertib combined with PD-1 and CTLA-4 blockade) compared to controls, suggesting that FSTL3 may be involved in immunotherapy resistance. In conclusion, this study suggests a role for FSTL3 as a prognostic marker and as therapeutic target in HGSOC, where it may play a role in promoting a mesenchymal tumor phenotype, maintaining an immunosuppressive tumor microenvironment, and driving immunotherapy resistance.

Furthermore, combining Prexasertib with 5-fluorouracil, a standard chemotherapeutic agent, produced a synergistic killing effect. These findings establish a novel synthetic lethal relationship between FBXO7 and CHEK1, suggesting that CHEK1 inhibition may provide a targeted therapeutic strategy for CRC patients with FBXO7 deficiencies, and highlighting the broader potential of exploiting SCF complex alterations in CRC therapy.

P1/2, N=30, Not yet recruiting, Australasian Leukaemia & Lymphoma Group

Strikingly, three HRP subtypes emerged, marked by unique structural alterations and gene expression patterns, tumor microenvironment interactions, and different chemotherapy responses. Finally, organoid experiments showed subtype-specific sensitivity to CHK1 inhibition, suggesting prexasertib as a potential targeted treatment for most currently untreatable HRP patients.

P2, N=353, Recruiting, Acrivon Therapeutics | Phase classification: P1/2 --> P2 | Trial completion date: Dec 2027 --> Apr 2027 | Trial primary completion date: Jul 2026 --> Oct 2026

A therapy with anti-N1/prexasertib could represent a novel treatment strategy, alone or in combination with current treatment regimens, for melanoma brain metastases.

In vivo, low-dose prexasertib exhibits immune-modulatory effects and synergizes safely with immune checkpoint blockade at subtherapeutic doses. Our findings establish reduced-dose CHK1 inhibition as a strategy to amplify immunotherapy efficacy while circumventing systemic toxicity, providing a translatable framework for optimizing therapeutic windows in clinical oncology.