saruparib (AZD5305)

P1/2, N=300, Not yet recruiting, AstraZeneca

We also identified and characterised a PARP1 mutation resulting in loss of the enzymatic inhibition and trapping activity of the PARP1-selective inhibitor, saruparib. However, the same mutation increased the trapping ability of other PARPi, namely veliparib and olaparib, without enhancing their enzymatic inhibition activity, a change that led to an increase in efficacy in this BRCA1m model. Together, these data suggest that PARP1 trapping, and not only its enzymatic inhibition, is a key driver for PARPi effectiveness in BRCA1m cancer cells.

P1, N=120, Recruiting, AstraZeneca | Trial completion date: Feb 2026 --> Aug 2026 | Trial primary completion date: Feb 2026 --> Aug 2026

P1/2, N=174, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

To address this, we generated in vitro prostate cancer models of acquired PARPi resistance to olaparib and saruparib, a novel selective PARP1 inhibitor and pursued functional characterization and drug sensitivity studies. Consistently, we demonstrate in vivo that the combination of PARPi-ATRi in resistant models restores treatment sensitivity through enhancing replication stress. Collectively, these findings highlight an interplay between ATM-ATR signaling as a key mediator of PARPi sensitivity in ATM-deficient mPC and identify a promising therapeutic combination to prolong treatment response and potentially improve patients' outcomes.

P1/2, N=30, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

In this study, we combined the structure of the latest second-generation selective PARP1 inhibitor AZD5305 to design and synthesize a series of second-generation selective PARP1/EZH2 dual inhibitors...Meanwhile, compared with the previous first-generation inhibitors, its permeability has improved, but its overall pharmacokinetic characteristics still need to be further optimized. However, as a novel selective PARP multifunctional molecule, it remains a highly promising potential compound for the for the treatment of TNBC.

P1/2, N=370, Recruiting, AstraZeneca | Trial completion date: Mar 2027 --> Sep 2027 | Trial primary completion date: Mar 2027 --> Sep 2027

P2, N=900, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

P1/2, N=30, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P1/2, N=175, Recruiting, AstraZeneca | Trial completion date: Apr 2026 --> Apr 2031 | Trial primary completion date: Apr 2026 --> Apr 2031

P3, N=700, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting