saruparib (AZD5305) / AstraZeneca - LARVOL DELTA

An Update on the CONCORDE study: A Phase Ib Platform Study of DNA Damage Repair Inhibitors (DDRis) in Combination With Conventional Radiotherapy in NSCLC (BTOG 2025) - P1 | "In 2 study arms, participants also receive consolidation durvalumab ±DDRi for up to 12 months...The primary objective is to assess safety and to determine the recommended phase II dose of each DDRi. Since 17/03/21, 4 arms have opened: A (olaparib, PARPi), B (AZD1390, ATMi), C (ceralasertib, ATRi) and E (saruparib, PARP-1i)... CONCORDE continues to recruit patients to three study arms (A,C,E). The platform demonstrated excellent capability in identifying excess toxicity in DDRi-RT combinations, leading to Arm–B closure. Analysis of patient-reported outcomes and efficacy are ongoing."

Combination therapy • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PARP1

TalaCom: Phase Ib investigator-initiated trial combining talazoparib and axitinib in patients with DNA damage response mutated cancers or BRCA1/2 wildtype ovarian cancer incorporating prospective intrapatient dose titration (ESMO-TAT 2025) - P1 | "22/24 (92%) evaluable pts achieved RECIST SD or PR; 13/24 (54%) had tumor regressions, and 5/24 (21%) achieved RECIST PRs: 2 pts with BRCA2m HGSOC (one who progressed on prior olaparib, saruparib and camonsertib); 1 pt with BRCA2m peritoneal mesothelioma; 2 pts with mCRPC without DDR mutations (one who progressed on prior olaparib). The combination of axi + tala was generally manageable with durable antitumor activity in heavily pretreated HGSOC and CRPC pts, including pts who progressed on prior PARPi. Biomarker and PK analyses are ongoing."

Clinical • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • High Grade Serous Ovarian Cancer • Mesothelioma • Oncology • Ovarian Cancer • Peritoneal Mesothelioma • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • BRIP1 • CDK12 • CHEK2 • PALB2 • RAD51C

ASCERTAIN: An open-label, randomized, phase 1, window-of-opportunity study to investigate the biological effects of AZD5305 and darolutamide alone or in combination in men with prostate cancer eligible for radical prostatectomy. (ASCO-GU 2024) - P1 | "The Phase 3 PROpel study showed that first-line combination treatment with olaparib and abiraterone significantly improved radiographic progression-free survival (rPFS) over abiraterone alone in pts with metastatic castration-resistant PC (mCRPC) (hazard ratio [HR], 0.66; 95% CI, 0.54 to 0.81; p<0.001). Similarly, the Phase 3 TALAPRO-2 study showed that first-line talazoparib with enzalutamide resulted in statistically significant improvement in rPFS over enzalutamide alone in pts with mCRPC (HR, 0.63; 95% CI, 0.51 to 0.78; p<0.0001)...Enrollment began in September 2023; sites across North America, Europe and Australia will enroll up to 120 patients. Clinical trial information: NCT05938270."

Clinical • P1 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • PARP2

Olaparib, AZD1390, ceralasertib, saruparib and consolidation durvalumab (CONCORDE) phase Ib platform study of novel DNA damage response inhibitor (DDRi) agents in combination with radiotherapy in non-small cell lung cancer (NSCLC). (ASCO 2024) - "A parallel multimodality translational program to identify biomarkers of treatment response, toxicity and the impact on the immune system are in development. Biomarkers of interest include plasma toxicity markers, immune cell profiling, radiomics and ctDNA."

Combination therapy • P1 data • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Saruparib: Data from P3 EvoPAR-Prostate01 trial (NCT06120491) for metastatic CSPC post 2027 (AstraZeneca) - FY 2025 Results: Data from P3 EvoPAR-Prostate02 trial (NCT06952803) for BRCAm prostate cancer post 2027

P3 data • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

Saruparib + camizestrant: Data from P3 EvoPAR-Breast01 trial (NCT06380751) for HR+/HER2-negative advanced breast cancer post 2027 (AstraZeneca) - FY 2025 Results

P3 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology

Saruparib: Data from P1 ASCERTAIN trial (NCT05938270) for newly diagnosed prostate cancer in H2 2026 (AstraZeneca) - FY 2025 Results

P1 data • Oncology • Prostate Cancer

Saruparib: Data from P1/2a PETRA trial (NCT04644068) for advanced solid malignancies in 2027 (AstraZeneca) - FY 2025 Results: Data from P1/2a PETRANHA trial (NCT05367440) for metastatic prostate cancer post 2027

P1/2 data • Oncology • Prostate Cancer • Solid Tumor

First interim efficacy analysis of the phase I/II PETRANHA trial of saruparib + androgen receptor pathway inhibitors (ARPI) in patients (pts) with metastatic prostate cancer (mPC) (ESMO 2025) - P1/2 | "Methods Pts, allocated by investigator choice, received saruparib 60 mg once daily (OD) + enzalutamide 160 mg OD (Arm 1), abiraterone 1000 mg OD + 5 mg prednisone OD or twice daily (BD; Arm 2), or darolutamide 600 mg BD (Arm 3) until disease progression or intolerable adverse event (AE)...Arm 4 (+ apalutamide 240 mg OD) is ongoing dose escalation and was not included in this analysis...EvoPAR-01 is an ongoing phase 3 study evaluating this combination in mCSPC. Table: 2384MO mCRPC Prior ARPI N=19 mCRPC ARPI-naïve N=31 mCSPC N=27 Median duration of saruparib / ARPI exposure, months (range) 5.5 (1.2–17.7) / 5.5 (1.1–17.7) 14.7 (0.3–24.8) / 15.7 (0.4–24.8) 17.8 (0.2–28.2) / 19.7 (0.2–28.2) Any AE, n (%) 18 (94.7) 31 (100) 26 (96.3) Any AE causally related to saruparib, n (%) 16 (84.2) 28 (90.3) 23 (85.2) Any AE Gr ≥3, n (%) 6 (31.6) 16 (51.6) 14 (51.9) Any serious AE, n (%) 4 (21.1) 10 (32.3) 4 (14.8) Saruparib / ARPI discontinuation due to AE, n (%) 1 (5.3) / 1..."

Clinical • Metastases • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

Phase III, randomized, double-blind, placebo-controlled study of adjuvant saruparib (AZD5305) in patients with BRCAm localized high-risk prostate cancer who are receiving radiotherapy and androgen deprivation therapy (EvoPAR-Prostate02). (ASCO-GU 2026) - P3 | "Clinical Trial Registry Number: NCT06952803. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Clinical • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Saruparib + androgen receptor pathway inhibitor (ARPI) + androgen deprivation therapy (ADT) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC): The phase 1/2 PETRANHA trial. (ASCO-GU 2026) - P1/2 | "Clinical Trial Registry Number: NCT05367440. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Clinical • Metastases • P1/2 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

PETRA: First in class, first in human trial of the next generation PARP1-selective inhibitor AZD5305 in patients (pts) with BRCA1/2, PALB2 or RAD51C/D mutations (AACR 2022) - P1/2 | "AZD5305 is a highly selective PARP1 inhibitor and trapper with excellent physiochemical properties and a wide therapeutic index. It led to maximal target engagement and showed promising clinical activity with favorable tolerability at exposures surpassing those of 1st generation PARPi. >"

Clinical • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRCA1 • BRCA2 • MUC16 • PALB2 • RAD51C • RAD51D

PETRA: first-in-human Phase 1/2a trial of the first-in-class new generation poly(ADP-ribose) polymerase-1 selective inhibitor (PARP1i) saruparib (AZD5305) in patients (pts) with advanced solid tumors with BRCA1/2, PALB2 or RAD51C/D mutations (AACR 2024) - P1/2 | "Saruparib showed very encouraging efficacy, a favorable safety profile, robust target engagement, and a wide therapeutic index. The RP2D was 60 mg QD, based on improved clinical efficacy and favorable safety profile, supported by substantial PK, PD and preclinical data.Table. Saruparib Safety and Efficacy at 60 mg QD*Patients with multiple events in the same category are counted only once in that category."

Clinical • Metastases • P1/2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRCA1 • BRCA2 • HER-2 • PALB2 • RAD51C • RAD51D

Phase III, double-blind, placebo-controlled, 2-cohort, randomized study of saruparib (AZD5305) in combination with new hormonal agents in patients with metastatic castration-sensitive prostate cancer with and without homologous recombination repair mutati (AUA 2024) - No abstract available

Clinical • Combination therapy • Metastases • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

ANDROMEDA: A Trial to Learn How Safe AZD9750 is and How Well it Works in People With Metastatic Prostate Cancer When Given With or Without Other Anticancer Drugs (clinicaltrials.gov) - P1/2 | N=300 | Not yet recruiting | Sponsor: AstraZeneca

First-in-human • Monotherapy • New P1/2 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Genetic evidence for PARP1 trapping as a driver of PARP inhibitor efficacy in BRCA mutant cancer cells. (PubMed, Nucleic Acids Res) - "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."

Journal • Breast Cancer • Oncology • Solid Tumor • BRCA • BRCA1 • HRD

PARP Activity Is Essential for Retinal Photoreceptor Survival in the Human Homologous RhoI255del Mouse Model for Autosomal Dominant Retinitis Pigmentosa. (PubMed, J Neurochem) - "The PARP inhibitors used -olaparib, saruparib, INO1001, and nicotinamide-target different PARP isoforms, and their potentially differential effects were evaluated in organotypic retinal explants cultivated under entirely defined conditions. On the other hand, cone photoreceptors were apparently unaffected by PARP inhibition. The present study thus demonstrates the importance of PARP activity for rod photoreceptor viability in a dominant rhodopsin mutant, highlights the need for a deeper understanding of the mechanisms underlying photoreceptor degeneration in different RP forms, and cautions against the indiscriminate use of PARP inhibitors for the treatment of RP."

Journal • Preclinical • CNS Disorders • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • CAPN2 • CASP3

ASCERTAIN: A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer. (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Feb 2026 ➔ Aug 2026 | Trial primary completion date: Feb 2026 ➔ Aug 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase 1/2a trial of new generation PARP1-selective inhibitor saruparib + next generation selective ER degrader (SERD) camizestrant in patients (pts) with advanced/relapsed ER+/HER2-negative or low (HER2−) breast cancer (PETRA Module 6) (SABCS 2025) - P1/2, P3 | "Pts could receive prior CDK4/6 inhibitors or fulvestrant, but not oral SERDs. Saruparib + camizestrant was well tolerated with no new safety signals versus prior monotherapy studies of each drug. PK of saruparib in combination with camizestrant was consistent with monotherapy data. Preliminary efficacy of the combination was promising and compared favorably with camizestrant monotherapy."

Clinical • Metastases • P1/2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • ER • HER-2 • PALB2

PETRANHA: Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer (clinicaltrials.gov) - P1/2 | N=174 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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 • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ATM • CHEK1 • HRD

Phase III study: saruparib + camizestrant vs CDK4/6i regimens in HR+/HER2– ABC with BRCA/PALB2 mutations (EvoPAR-Breast01) (ABC8 2025) - No abstract available

P3 data • Oncology • BRCA • CDK4 • HER-2 • PALB2

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 | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Biomarker • Enrollment closed • Monotherapy • Oncology • Ovarian Cancer • Solid Tumor

A randomized phase III study of first-line saruparib (AZD5305) plus camizestrant vs CDK4/6i plus physician's choice endocrine therapy or CDK4/6i plus camizestrant in patients with HR+/HER2− advanced breast cancer with BRCA1/BRCA2/PALB2 mutations (EvoPAR-Breast01) (DGHO 2025) - P3 | "Participants will be randomized 2:2:1 to receive saruparib plus camizestrant, physician's choice CDK4/6i (abemaciclib, ribociclib, or palbociclib) plus physician's choice ET (fulvestrant, letrozole, anastrozole, or exemestane), or physician's choice CDK4/6i plus camizestrant, respectively. Overall survival (OS) is a secondary endpoint. Approximately 500 participants will be randomized."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • CDK4 • HER-2 • HRD • PALB2

Saruparib: Data from P1/2 trial (NCT07060365) for newly diagnosed BRCA1/2m advanced/recurrent ovarian cancer post 2026 (AstraZeneca) - Q3 2025 Results

P1/2 data • Oncology • Ovarian Cancer