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    DRUG:

    saruparib (AZD5305)

    i
    Other names: AZD5305, AZD-5305, AZD 5305
    Company:
    AstraZeneca
    Drug class:
    PARP1 inhibitor
    Related drugs:
    8d
    Combination therapy overcomes secondary PARPi resistance in ATM-deficient prostate cancer. (PubMed, NPJ Precis Oncol)
    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.
    Journal
    |
    ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CHEK1 (Checkpoint kinase 1)
    |
    Lynparza (olaparib) • saruparib (AZD5305)
    14d
    A Master Protocol Study to Investigate Biomarker-guided Novel Anticancer Agent(s) as Monotherapy or Combination Therapy in Participants With Advanced/Recurrent Ovarian Cancer (clinicaltrials.gov)
    P1/2, N=30, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    saruparib (AZD5305)
    1m
    Discovery of selective PARP1/EZH2 inhibitor inducing PANoptosis in triple-negative breast cancer. (PubMed, Eur J Med Chem)
    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.
    Journal
    |
    PARP2 (Poly(ADP-Ribose) Polymerase 2)
    |
    saruparib (AZD5305)
    2ms
    BLUESTAR: A Phase I/IIa Study of AZD8205 Given Alone or in Combination With Anticancer Drugs, in Participants With Advanced or Metastatic Solid Malignancies (clinicaltrials.gov)
    P1/2, N=370, Recruiting, AstraZeneca | Trial completion date: Mar 2027 --> Sep 2027 | Trial primary completion date: Mar 2027 --> Sep 2027
    Trial completion date • Trial primary completion date
    |
    puxitatug samrotecan (AZD8205) • saruparib (AZD5305) • rilvegostomig (AZD2936)
    2ms
    S2409: Using Biomarker Tests to Select and Test New, Personalized Treatments for Extensive Stage Small Cell Lung Cancer, PRISM Study (clinicaltrials.gov)
    P2, N=900, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting
    Enrollment open
    |
    SLFN11 (Schlafen Family Member 11)
    |
    Imfinzi (durvalumab) • etoposide IV • ceralasertib (AZD6738) • saruparib (AZD5305) • monalizumab (IPH2201)
    2ms
    A Master Protocol Study to Investigate Biomarker-guided Novel Anticancer Agent(s) as Monotherapy or Combination Therapy in Participants With Advanced/Recurrent Ovarian Cancer (clinicaltrials.gov)
    P1/2, N=30, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting
    Enrollment open
    |
    saruparib (AZD5305)
    2ms
    PETRANHA: Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer (clinicaltrials.gov)
    P1/2, N=175, Recruiting, AstraZeneca | Trial completion date: Apr 2026 --> Apr 2031 | Trial primary completion date: Apr 2026 --> Apr 2031
    Trial completion date • Trial primary completion date
    |
    Xtandi (enzalutamide) • abiraterone acetate • Nubeqa (darolutamide) • apalutamide • saruparib (AZD5305)
    3ms
    EvoPAR-PR02: A Study of Metastases Free Survival With Saruparib vs Placebo Added to a Standard RT/ADT in Men With High-risk Prostate Cancer With a BRCA Mutation (clinicaltrials.gov)
    P3, N=700, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting
    Enrollment open
    |
    BRCA (Breast cancer early onset)
    |
    abiraterone acetate • prednisone • saruparib (AZD5305)
    3ms
    PETRA: Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=702, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    carboplatin • paclitaxel • Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan-dlnk) • camizestrant (AZD9833) • saruparib (AZD5305)
    4ms
    PETRANHA: Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer (clinicaltrials.gov)
    P1/2, N=175, Recruiting, AstraZeneca | Trial completion date: Apr 2031 --> Apr 2026 | Trial primary completion date: Apr 2031 --> Apr 2026
    Trial completion date • Trial primary completion date
    |
    Xtandi (enzalutamide) • abiraterone acetate • Nubeqa (darolutamide) • apalutamide • saruparib (AZD5305)
    5ms
    A Master Protocol Study to Investigate Biomarker-guided Novel Anticancer Agent(s) as Monotherapy or Combination Therapy in Participants With Advanced/Recurrent Ovarian Cancer (clinicaltrials.gov)
    P1/2, N=30, Not yet recruiting, AstraZeneca
    New P1/2 trial
    |
    saruparib (AZD5305)
    5ms
    PETRA: Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=804, Recruiting, AstraZeneca | Trial completion date: Mar 2027 --> Jun 2027 | Trial primary completion date: Mar 2027 --> Jun 2027
    Trial completion date • Trial primary completion date
    |
    carboplatin • paclitaxel • Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan-dlnk) • camizestrant (AZD9833) • saruparib (AZD5305)