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Last updated: June 22, 2026
PARP (poly ADP-ribose polymerase) is a family of enzymes that detects single-strand DNA breaks and recruits the base-excision repair machinery to fix them. A PARP inhibitor is a small-molecule oral drug that blocks PARP1 (and usually PARP2) catalytic activity and traps PARP on the DNA, converting unrepaired single-strand breaks into double-strand breaks during replication.
The selective killing of PARPi-exposed cancer cells with deficient DNA repair is called synthetic lethality:
Olaparib was the first PARP inhibitor approved by the FDA (December 2014, BRCA-mutated ovarian), opening the synthetic-lethality drug class. Four PARPi are now FDA-approved across ovarian, BRCA-mutated breast, BRCA-mutated mCRPC and HRR-mutated mCRPC, and BRCA/PALB2 pancreatic maintenance. Next-generation PARP1-selective agents like saruparib (AZD5305) aim to keep talazoparib-like potency at PARP1 while sparing PARP2 to reduce on-target anemia/neutropenia/thrombocytopenia.
| Drug | Sponsor | Class | Regulatory Status | Trials in Corpus |
|---|---|---|---|---|
| Olaparib (Lynparza, AZD2281) | AstraZeneca / Merck | PARP1/2 inhibitor (first-in-class) | FDA Dec 2014: BRCA-mutated advanced ovarian (first PARPi). FDA Jan 2018: BRCA-mutated metastatic breast (OlympiAD). FDA Dec 2019: gBRCA metastatic pancreatic maintenance (POLO). FDA May 2020: BRCA-mutated mCRPC (PROfound). | 123 trials (17 Phase 3 recruiting) |
| Niraparib (Zejula, MK-4827) | GSK / Janssen | PARP1/2 inhibitor | FDA Mar 2017: recurrent ovarian maintenance (NOVA). FDA Apr 2020: 1L ovarian maintenance regardless of BRCA status (PRIMA) — first PARPi approved without a BRCA biomarker requirement. FDA Apr 2023: prostate combination indications. | 44 trials (10 Phase 3 recruiting) |
| Talazoparib (Talzenna, BMN 673) | Pfizer | PARP1/2 inhibitor (most potent PARP-trapper) | FDA Oct 2018: gBRCA HER2-negative metastatic breast (EMBRACA). FDA Jun 2023: HRR-mutated mCRPC + enzalutamide (TALAPRO-2). | 32 trials (1 Phase 3 recruiting) |
| Rucaparib (Rubraca) | pharma& (formerly Clovis Oncology, IP acquired 2022) | PARP1/2 inhibitor | FDA Dec 2016: BRCA-mutated advanced ovarian. FDA May 2020: BRCA-mutated mCRPC. Phase 3 program smaller after Clovis bankruptcy. | 13 trials (3 Phase 3 recruiting) |
| Saruparib (AZD5305) | AstraZeneca | Next-gen PARP1-selective inhibitor | Investigational. PARP1-selective design intended to spare PARP2-mediated hematologic toxicity. Active Phase 3 in BRCA mCRPC (saruparib + RT/ADT, MFS) and HR+/HER2- BRCA breast (saruparib + camizestrant vs CDK4/6i + ET). | 11 trials (2 Phase 3 recruiting) |
| Fluzoparib (SHR-3162) | Jiangsu Hengrui | PARP1/2 inhibitor | NMPA-approved 2020 (China): BRCA-mutated ovarian and platinum-sensitive recurrent ovarian maintenance. Not FDA-approved. | 21 trials (4 Phase 3 recruiting) |
| Pamiparib (BGB-290) | BeiGene | PARP1/2 inhibitor | NMPA-approved (China): ovarian, prostate. Not FDA-approved. Smaller Phase 3 program. | 4 trials (1 Phase 3 recruiting) |
The first-in-class PARP inhibitor and the broadest in regulatory footprint. FDA December 2014 for BRCA-mutated advanced ovarian cancer — the first PARP inhibitor approved by the FDA — followed by FDA January 2018 for BRCA-mutated HER2-negative metastatic breast cancer (OlympiAD), FDA December 2019 for germline BRCA-mutated metastatic pancreatic cancer maintenance (POLO — the first targeted maintenance therapy in pancreatic), and FDA May 2020 for BRCA-mutated metastatic castration-resistant prostate cancer (PROfound). PAOLA-1 established olaparib + bevacizumab as 1L ovarian maintenance in HRD-positive disease; SOLO-2 established olaparib monotherapy maintenance in BRCA-mutated platinum-sensitive recurrent ovarian; OlympiA established adjuvant olaparib in high-risk early-stage gBRCA breast. Key Phase 3 trials in the corpus: NCT06580314 (testing olaparib for 1 or 2 years, with or without bevacizumab, in ovarian); NCT06712472 (maintenance olaparib vs observation after adjuvant chemoradiotherapy in p53abn endometrial — a new disease indication for the class); NCT06095141 (cisplatin in pancreatic patients with HRD).
GSK's PARP inhibitor (Janssen holds prostate rights). FDA March 2017 for recurrent ovarian cancer maintenance after platinum response (NOVA), and FDA April 2020 for advanced ovarian cancer first-line maintenance regardless of BRCA status (PRIMA) — the first PARPi approved without a BRCA biomarker requirement, though HRD-positive subgroups derive larger benefit. QUADRA established niraparib activity in platinum-sensitive ovarian. Once-daily oral dosing. Distinct pharmacology: high brain penetration (driving the GBM Phase 3 program) but also a thrombocytopenia signal that prompted weight- and platelet-based starting dose adjustment. Key Phase 3 trials in the corpus: NCT05659381 (hyperthermic intraperitoneal chemotherapy [HIPEC] followed by niraparib in ovarian, primary peritoneal, fallopian tube); NCT05009082 (niraparib vs niraparib + bevacizumab in platinum/taxane-treated ovarian); NCT03651206 (niraparib + PD-1 inhibitor in recurrent ovarian carcinosarcoma); NCT06388733 (niraparib vs temozolomide in newly-diagnosed MGMT-unmethylated glioblastoma — the first PARP Phase 3 in glioma, leveraging niraparib's blood-brain-barrier penetration).
Pfizer's PARP inhibitor (acquired via Medivation/BioMarin), the most potent PARP-trapper in the class — talazoparib stabilizes the PARP-DNA complex on chromatin more strongly than other PARPi, which underlies both its high single-agent potency at low milligram doses (1 mg daily) and its on-target hematologic toxicity. FDA October 2018 for germline BRCA-mutated HER2-negative locally advanced/metastatic breast cancer (EMBRACA), establishing single-agent PARPi as standard 1L therapy in gBRCA breast. FDA June 2023 in combination with enzalutamide for HRR-mutated metastatic castration-resistant prostate cancer (TALAPRO-2) — the first PARPi + AR-pathway inhibitor combination approval in 1L mCRPC, expanding from BRCA-only to the broader HRR gene panel (BRCA1, BRCA2, ATM, PALB2, and others). Talazoparib's distinct potency profile makes it the typical comparator for next-generation PARP1-selective drugs.
Clovis Oncology's original PARP inhibitor, FDA December 2016 for BRCA-mutated advanced ovarian cancer (after two prior chemotherapies) and FDA May 2020 for BRCA-mutated metastatic castration-resistant prostate cancer (TRITON3). After Clovis Oncology's December 2022 bankruptcy, the rucaparib intellectual property and active trials were acquired by pharma& (formerly Pharma&, an Italian rare-disease and oncology specialty pharma). The Phase 3 program is smaller than for olaparib, niraparib, or talazoparib, but rucaparib remains an FDA-approved option in BRCA-mutated ovarian and mCRPC. ARIEL3 established rucaparib maintenance in platinum-sensitive recurrent ovarian. Combination studies with checkpoint inhibitors and chemotherapy continue under pharma&'s development plan.
AstraZeneca's next-generation PARP inhibitor and the most clinically advanced PARP1-selective agent. The therapeutic hypothesis: PARP1 inhibition is sufficient for synthetic-lethal killing of HR-deficient cancer cells, while PARP2 inhibition (the major driver of olaparib/niraparib/talazoparib hematologic toxicity in normal bone marrow) is what limits dosing and tolerability. By sparing PARP2, saruparib aims to deliver olaparib- or talazoparib-class anti-tumor activity at a substantially better tolerability profile, particularly for combination regimens. Key Phase 3 trials in the corpus: NCT06952803 (saruparib vs placebo added to standard RT/ADT in high-risk BRCA-mutated localized prostate cancer, metastasis-free survival endpoint — the first PARPi Phase 3 in localized prostate); NCT06380751 (saruparib + camizestrant vs CDK4/6 inhibitor + endocrine therapy in HR+/HER2- BRCA-mutated advanced breast — a cross-mechanism head-to-head against the current CDK4/6 hub standard of care, see /mechanisms/cdk4-6-inhibitors).
Jiangsu Hengrui's oral PARP inhibitor, NMPA-approved 2020 for BRCA-mutated platinum-sensitive recurrent ovarian cancer (third-line+) and as platinum-sensitive recurrent ovarian maintenance. Subsequent NMPA approvals in breast and gastric cancer settings. Not FDA-approved. Fluzoparib anchors a sizable China-led Phase 3 program (4 Phase 3 trials in the corpus), often combined with the Hengrui angiogenesis inhibitor apatinib or with bevacizumab. Key Phase 3 trials in the corpus: NCT06255392 (fluzoparib + apatinib vs investigator's choice); NCT06954584 (fluzoparib + bevacizumab vs fluzoparib monotherapy as 1L maintenance in HRD-positive and HRD-negative ovarian — an HRD-agnostic maintenance design comparable to PRIMA).
BeiGene's oral PARP inhibitor, NMPA-approved in China for BRCA-mutated platinum-sensitive recurrent ovarian cancer. Not FDA-approved. Pamiparib has a smaller Phase 3 program than fluzoparib, reflecting BeiGene's broader portfolio prioritization toward tislelizumab and other hematologic and IO assets. Combination trials with tislelizumab (BeiGene's PD-1) in HRD or BRCA-mutated solid tumors continue, with limited late-stage breadth.
The 328 recruiting (and 85 not-yet-recruiting) PARP inhibitor trials span the broadest cross-cancer distribution of any mechanism hub on this site. Phase 3 footprint by disease: breast 12, ovarian 9, prostate 7, pancreatic 3, endometrial 2, biliary 1, glioma 1. PARP inhibitors began as an ovarian-only class but, with BRCA testing now routine across multiple tumor types, are now being studied as a true cross-cancer synthetic-lethality platform.
Ovarian cancer is where PARP inhibitors were born (olaparib FDA Dec 2014, BRCA-mutated). The current Phase 3 frontier is HRD-agnostic 1L maintenance (PRIMA-style), maintenance combinations with bevacizumab (PAOLA-1 extensions), and intraperitoneal regional therapy with HIPEC + niraparib.
Breast cancer is now the single largest Phase 3 disease for the PARP class, driven by BRCA-mutated metastatic (talazoparib EMBRACA + olaparib OlympiAD), adjuvant high-risk gBRCA early breast (OlympiA), and the new saruparib + camizestrant cross-class head-to-head against CDK4/6i + endocrine therapy in HR+/HER2- BRCA breast.
Adjuvant olaparib in high-risk early-stage gBRCA breast (OlympiA, FDA 2022) and BRCA-mutated metastatic talazoparib monotherapy (EMBRACA, FDA Oct 2018) and BRCA-mutated metastatic olaparib monotherapy (OlympiAD, FDA Jan 2018) are the existing approvals anchoring this 12-Phase-3 disease footprint.
Olaparib (PROfound, FDA May 2020) and rucaparib (TRITON3, FDA May 2020) anchored BRCA-mutated mCRPC. Talazoparib + enzalutamide (TALAPRO-2, FDA Jun 2023) expanded into HRR-mutated 1L mCRPC and shifted the class from BRCA-only to the broader HRR gene panel. Saruparib + RT/ADT in localized BRCA-mutated high-risk prostate is the first PARPi attempt to move into curative-intent prostate therapy.
The POLO trial (olaparib maintenance after platinum-responsive 1L metastatic gBRCA pancreatic) led to FDA Dec 2019 approval — the first targeted maintenance therapy in pancreatic cancer. Subsequent Phase 3 trials are expanding the BRCA/PALB2 platinum-sensitivity story.
Endometrial is a new PARPi disease and is anchored by the molecular-classification subgroup analysis: p53-abnormal (p53abn) endometrial behaves like high-grade serous ovarian and is HRD-enriched, providing the biologic rationale for olaparib maintenance after adjuvant chemoradiotherapy.
Niraparib's brain penetration and BRCA/HRD pan-cancer prevalence are now opening previously unreachable diseases to PARP inhibitors.
Showing curated Phase 3 highlights from 328 RECRUITING + 85 not-yet-recruiting PARP inhibitor interventional trials in the ClinTrialFinder corpus as of June 22, 2026 (52 Phase 3 across the class; per-disease Phase 3 breakdown: breast 12, ovarian 9, prostate 7, pancreatic 3, endometrial 2, biliary 1, glioma 1). For the latest searches: olaparib, niraparib, talazoparib, rucaparib, saruparib, fluzoparib.
Acquired resistance to PARP inhibitors is the dominant clinical problem in long-responder PARPi-treated patients (especially BRCA-mutated ovarian on multi-year maintenance). The four main resistance mechanisms are:
Next-generation strategies in development:
A pragmatic clinical trend is sending circulating tumor DNA at PARPi progression to test for BRCA reversion mutations — if reversion is detected, the patient is typically platinum-resistant and unlikely to benefit from re-challenge, redirecting them to chemo, ADCs (in breast), Lu-177 PSMA-617 (in mCRPC), or trial enrollment in PARG/POLQ/WEE1 programs.
What is a PARP inhibitor and how does it work?
PARP (poly ADP-ribose polymerase) detects single-strand DNA breaks and recruits base-excision repair machinery. A PARP inhibitor blocks PARP1/2 catalytic activity and traps PARP on DNA, converting unrepaired single-strand breaks into double-strand breaks during replication. Normal cells repair these via homologous recombination (HR), which depends on BRCA1, BRCA2, PALB2, RAD51. Cancer cells with deficient HR — most commonly germline or somatic BRCA1/2 mutations, but also broader homologous recombination deficiency (HRD) — cannot repair the resulting double-strand breaks and die. This is called synthetic lethality and is the central mechanism of all approved PARP inhibitors.
Which PARP inhibitors are FDA-approved?
Olaparib (Lynparza, AstraZeneca/Merck): FDA Dec 2014 BRCA-mutated ovarian (first PARPi); FDA Jan 2018 BRCA-mutated metastatic breast (OlympiAD); FDA Dec 2019 gBRCA metastatic pancreatic maintenance (POLO); FDA May 2020 BRCA-mutated mCRPC (PROfound). Niraparib (Zejula, GSK/Janssen): FDA Mar 2017 recurrent ovarian maintenance (NOVA); FDA Apr 2020 1L ovarian maintenance regardless of BRCA status (PRIMA) — first PARPi without a BRCA biomarker requirement. Rucaparib (Rubraca, pharma&): FDA Dec 2016 BRCA-mutated ovarian; FDA May 2020 BRCA-mutated mCRPC. Talazoparib (Talzenna, Pfizer): FDA Oct 2018 gBRCA HER2-negative metastatic breast (EMBRACA); FDA Jun 2023 HRR-mutated mCRPC + enzalutamide (TALAPRO-2). Fluzoparib (Hengrui) and pamiparib (BeiGene) are NMPA-approved in China but not FDA-approved. Consult current FDA prescribing information.
Do I need BRCA testing to be eligible for a PARP inhibitor trial?
It depends on the trial. BRCA required: most BRCA-mutated breast and mCRPC PARPi trials require confirmed germline or somatic BRCA1/2, including saruparib + RT/ADT prostate (NCT06952803) and saruparib + camizestrant breast (NCT06380751). HRR-positive accepted: many prostate trials accept the broader HRR gene panel (BRCA1, BRCA2, ATM, PALB2, CHEK2, RAD51 family, FANCA), reflecting the TALAPRO-2 indication. HRD-agnostic: many ovarian 1L maintenance trials accept any patient regardless of BRCA/HRD (PRIMA-style), though HRD-positive subgroups derive larger benefit. BRCA/PALB2 only: pancreatic PARPi trials typically require germline BRCA1/2 or PALB2. As the field shifts toward HRD score-based eligibility (Myriad MyChoice CDx, FoundationOne CDx HRD), tumor sequencing increasingly drives entry regardless of germline status. Read the trial's specific inclusion criteria.
What's the difference between olaparib (Lynparza) and talazoparib (Talzenna)?
Potency and trapping: talazoparib is the most potent PARP-trapper in the class — it stabilizes the PARP-DNA complex on chromatin more strongly than other PARPi, converting more single-strand breaks into double-strand breaks. This drives both its high single-agent potency at low milligram doses (1 mg daily for Talzenna vs 300 mg twice daily for Lynparza) and its on-target hematologic toxicity (anemia, neutropenia, thrombocytopenia). FDA breadth: olaparib has the broader indication map (ovarian + breast + mCRPC + pancreatic) and the deepest combination dataset (PAOLA-1 olaparib + bev ovarian; PROpel olaparib + abiraterone mCRPC). Talazoparib niches: BRCA-mutated metastatic breast monotherapy (EMBRACA, FDA Oct 2018) and HRR-mutated mCRPC + enzalutamide (TALAPRO-2, FDA Jun 2023). Next-generation PARP1-selective drugs (saruparib AZD5305) aim to keep talazoparib-like potency at PARP1 while sparing PARP2 to reduce hematologic toxicity.
What is HRD (homologous recombination deficiency) and how is it measured?
HRD is a tumor phenotype where the cell cannot accurately repair double-strand DNA breaks because one or more HR pathway genes are inactivated. BRCA1 and BRCA2 mutations are the prototypical drivers, but HRD also encompasses PALB2, RAD51 family, BRIP1, BARD1, FANCA mutations and BRCA1 promoter methylation. Two FDA-cleared companion diagnostics measure HRD: Myriad MyChoice CDx (PAOLA-1 olaparib + bev ovarian; PRIMA niraparib ovarian) scores genomic instability via loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions, with an HRD-positive threshold; FoundationOne CDx HRD (PROfound mCRPC, several breast trials) reports a similar genomic scar with a different threshold. Newer functional assays measure RAD51 foci formation after DNA damage as a direct readout of HR competency. HRD-positive non-BRCA tumors derive PARPi benefit but typically smaller than BRCA-mutated tumors; HRD-negative tumors derive less benefit and are usually only eligible for HRD-agnostic ovarian 1L maintenance trials.
What happens after PARP inhibitor progression? What are the post-PARPi options?
Progression on PARPi most often reflects acquired resistance via (1) BRCA reversion mutations — the most common — restoring BRCA1/2 reading frame; (2) HR pathway restoration via 53BP1/REV7/Shieldin loss; (3) drug efflux via P-glycoprotein upregulation; or (4) PARP1 binding-site mutations. Post-PARPi options by tumor type: ovarian + BRCA breast — platinum re-challenge if platinum-sensitive (BRCA-reversion tumors are typically also platinum-resistant); mCRPC — taxanes (docetaxel, cabazitaxel), Lu-177 PSMA-617 Pluvicto (see /mechanisms/psma-radioligand-therapy), radium-223; pancreatic — gemcitabine + nab-paclitaxel or FOLFIRINOX. Phase 3 strategies to overcome PARPi resistance include PARG inhibitors, POLQ inhibitors (targeting the alternative end-joining backup pathway), WEE1 inhibitors (azenosertib), and ATR + PARPi combinations. Sending circulating tumor DNA at progression to test for BRCA reversion is increasingly part of treatment selection.
Find Matching PARP Inhibitor Trials
Use ClinTrialFinder's AI-powered matching to find olaparib (Lynparza), niraparib (Zejula), rucaparib (Rubraca), talazoparib (Talzenna), saruparib (AZD5305), fluzoparib, pamiparib, and next-generation PARP inhibitor trials based on your cancer type, BRCA1/2 status (germline or somatic), HRD score, HRR panel, prior PARPi exposure, and country.
Find Matching PARP Inhibitor TrialsThis page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your medical oncologist. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here. FDA approval dates and indications are summarized for context only; consult the current FDA prescribing information for each drug for authoritative regulatory status.