tuvusertib (M1774)

P2, N=56, Recruiting, Grupo Español de Investigación en Neurooncología

P2, N=63, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2028 --> Jun 2026 | Trial primary completion date: Jan 2028 --> Sep 2025

P1/2, N=56, Recruiting, Grupo Espanol De Investigacion En Neurooncologia

Both tuvusertib and olaparib induced stronger radiosensitization than xevinapant and combining both agents resulted in especially profound radiosensitization in three out of the four cell lines tested, whereas their combination with xevinapant or the combination of xevinapant with cisplatin was less effective. Assessment of cell death induction via annexin V/DAPI staining failed to generally predict cytotoxicity or radiosensitization of these approaches. Overall, our data are in line with the recent failure of the phase 3 TrilynX trial and suggest further investigation of ATR and PARP inhibition for the curative treatment of HPV-negative HNSCC.

P1, N=161, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

P1, N=10, Terminated, Institut Curie | N=92 --> 10 | Trial completion date: Sep 2029 --> Nov 2025 | Recruiting --> Terminated | Trial primary completion date: Sep 2028 --> Nov 2025; Although no safety signal has been observed, given that the industrial development of tuvusertib has been halted regardless of the results, we see no scientific and ethical justification for continuing the study

P1, N=141, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting

Enhanced avelumab-mediated antibody-dependent cell-mediated cytotoxicity and lysis by PD-L1 targeting high-affinity NK (PD-L1 t-haNK) cells were observed in tuvusertib-treated DU145. In vivo in the DU145 PCa xenograft model, tuvusertib and N-803 combination therapy demonstrated marked and significant antitumor efficacy relative to either monotherapy, eliciting superior tumor growth control and prolonging survival. Our findings support further investigation into the use of ATRi with immune checkpoint blockade and/or immune-stimulating agents in prostate cancer.

P1, N=12, Active, not recruiting, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Recruiting --> Active, not recruiting

P1, N=120, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting

P2, N=63, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting | N=130 --> 63

The analysis supports tuvusertib 180 mg QD 2w on/1w off as the RDE and 100 mg QD as the no-regret dose for clinical evaluation. This example underscores the value of integrated quantitative pharmacology analyses to inform dose selection using a totality of evidence approach.