Key Phase 3 Trials: Prostate Cancer
| Trial | Drug / Regimen | Sponsor | Setting | Status |
|---|---|---|---|---|
| NCT03732820 PROpel | Olaparib + Abiraterone | AstraZeneca | 1L mCRPC | Active Phase 3 |
| NCT05171816 | Olaparib + Abiraterone (China) | AstraZeneca | 1L mCRPC | Active Phase 3 |
| NCT03395197 TALAPRO-2 | Talazoparib + Enzalutamide | Pfizer | 1L mCRPC (HRR-mutated) | Active Phase 3 |
| NCT04821622 TALAPRO-3 | Talazoparib + Enzalutamide | Pfizer | 1L mCSPC (DDR-mutated) | Active Phase 3 |
| NCT03748641 | Niraparib + Abiraterone | Janssen | 1L mCRPC | Active Phase 3 |
| NCT04497844 | Niraparib + Abiraterone | Janssen | 1L mCSPC (HRR-mutated) | Active Phase 3 |
| NCT04455750 | Rucaparib + Enzalutamide | Alliance (NCI) | mCRPC (HRR-mutated) | Active Phase 3 |
Key Phase 3 Trials: Ovarian and Breast Cancer
| Trial | Drug / Regimen | Sponsor | Setting | Status |
|---|---|---|---|---|
| NCT02032823 OlympiA | Olaparib (adjuvant) | AstraZeneca | gBRCA HER2- early breast cancer | Active Phase 3 |
| NCT06580314 | Olaparib ± Bevacizumab | NRG Oncology | Ovarian cancer maintenance (1–2 yrs) | Recruiting Phase 3 |
| NCT02655016 PRIMA/ENGOT-OV26 | Niraparib maintenance | GSK/Tesaro | Advanced ovarian, 1L platinum response | Active Phase 3 |
| NCT03602859 | Niraparib + TSR-042 vs SOC | GSK/Tesaro | Advanced ovarian, 1L platinum | Active Phase 3 |
| NCT04475939 | Niraparib + Pembrolizumab maintenance | GSK | Advanced/mNSCLC maintenance | Active Phase 3 |
Key Phase 3 Trials: Endometrial and Emerging Indications
| Trial | Drug / Regimen | Sponsor | Setting | Status |
|---|---|---|---|---|
| NCT06712472 | Olaparib maintenance vs observation | Gustave Roussy | Adjuvant p53abn endometrial cancer | Recruiting Phase 3 |
| NCT06746116 | Durvalumab + chemo → Durvalumab + Olaparib | AstraZeneca | Advanced/recurrent endometrial cancer | Active Phase 3 |
| NCT06388733 | Niraparib vs Temozolomide | Ivy Brain Tumor Center | MGMT-unmethylated GBM | Recruiting Phase 3 |
The PARP Inhibitor Class: Mechanism and Differentiation
PARP inhibitors exploit a concept called synthetic lethality: in cells with impaired homologous recombination (typically BRCA1/2 mutations or broader HRD), inhibiting PARP1/2 creates DNA lesions that cannot be repaired, causing selective cancer cell death while sparing normal cells. The mechanism has proven durable across a decade of clinical development because it targets an intrinsic DNA repair vulnerability rather than a specific driver mutation.
The Four Commercial Agents Compared
- Olaparib (AstraZeneca — Lynparza): First approved (2014), broadest label. Current approvals: ovarian (1L maintenance, 2L maintenance, treatment), breast (gBRCA HER2-), prostate (HRR-mutated mCRPC + abiraterone, BRCA-mutated mCRPC), endometrial (dMMR + durvalumab), pancreatic (gBRCA maintenance). Moderate PARP trapping potency. Twice-daily oral dosing. Strategic asset: AZ runs joint development with MSD (Merck) for many combination programs.
- Niraparib (GSK — Zejula, formerly Tesaro/J&J): Ovarian and prostate approvals. Differential: biomarker-agnostic niraparib maintenance approval in ovarian cancer (FDA 2020) — does not require BRCA or HRD testing. Once-daily oral dosing. Thrombocytopenia is the key dose-limiting toxicity, managed with individualized starting doses. Now wholly owned by GSK following J&J spin strategy.
- Talazoparib (Pfizer — Talzenna): Highest PARP trapping potency in class (~100-fold vs veliparib). Approvals: gBRCA HER2- metastatic breast cancer (2018); HRR-mutated mCRPC + enzalutamide (2023 — TALAPRO-2). High trapping translates to deep responses but significant hematological toxicity (anemia, thrombocytopenia).
- Rucaparib (Clovis, then Pfizer): Clovis filed for bankruptcy in 2022; Pfizer acquired rucaparib assets. FDA approval for BRCA-mutated ovarian cancer treatment/maintenance and BRCA-mutated mCRPC. Actively enrolled trials being managed by Pfizer-assigned academic partners and NCI.
AstraZeneca's Olaparib Empire
AstraZeneca has built the most diverse PARP inhibitor clinical franchise by combining olaparib with its own and partner molecules across every solid tumor where HRD enrichment is plausible:
- Olaparib + durvalumab (PD-L1): DUO-E approval in dMMR endometrial cancer (2023). Multiple trials testing in ovarian, NSCLC, SCLC, and TNBC.
- Olaparib + abiraterone: PROpel FDA approval (2023) in 1L mCRPC — initially all-comers, later HRR-enriched label following ODAC review.
- OlympiA: Olaparib adjuvant in gBRCA HER2-negative early breast cancer — established the first adjuvant PARPi approval and the first demonstration of PARPi survival benefit in early disease.
AstraZeneca's strategy is breadth: use olaparib as the backbone for combination strategies across tumor types, building a franchise that extends beyond the initial HRD-enriched ovarian cancer beachhead. Monitoring new olaparib combination registrations is critical intelligence for any oncology BD team.
PARP Inhibitors in Prostate Cancer: The Race for Combination Dominance
The prostate cancer PARP inhibitor market has become one of the most competitive in oncology. Four different PARPi+AR inhibitor combinations have received FDA approval or are in Phase 3:
- Olaparib + abiraterone (PROpel, AstraZeneca) — Phase 3 approved 2023, all HRR-mutated mCRPC
- Talazoparib + enzalutamide (TALAPRO-2, Pfizer) — Phase 3 approved 2023, HRR-mutated mCRPC; TALAPRO-3 in HRR-mutated mCSPC ongoing
- Niraparib + abiraterone (MAGNITUDE, Janssen) — Phase 3 approved 2023, HRR-mutated mCRPC
- Rucaparib + enzalutamide (Alliance/NCI) — Phase 3 ongoing
The competitive question: with four approved or late-stage options, differentiation will shift to biomarker depth (BRCA1/2 only vs broader HRR), safety profile (hematological vs metabolic toxicity), and combinations with next-generation AR inhibitors (enzalutamide, apalutamide, darolutamide). BD teams evaluating prostate assets must track head-to-head data as it emerges.
Related Drug Class and Indication Pages
- Ovarian Cancer Clinical Trials — Full Landscape
- Prostate Cancer Clinical Trials
- Breast Cancer Clinical Trials
- Endometrial Cancer Clinical Trials
- HER2-Positive Breast Cancer Clinical Trials
- Pancreatic Cancer Clinical Trials
Monitor PARP Inhibitor Trials Daily — Free
Get notified when new PARP inhibitor trials register, Phase 3 enrollment opens, or status changes on existing programs. Track olaparib, niraparib, or talazoparib across all indications.
Start Free Trial →Frequently Asked Questions
What HRR gene mutations predict PARP inhibitor benefit?
BRCA1 and BRCA2 mutations carry the strongest evidence for PARP inhibitor benefit across tumor types. The broader HRR panel includes: ATM, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B/C/D, and RAD54L. CDK12 mutations are a special case — they cause impaired HRR through a different mechanism (tandem duplication phenotype) and clinical data on CDK12-mutated prostate cancer show differential responses. Regulatory guidance has evolved from BRCA-only to HRR-expanded labeling as Phase 3 datasets mature.
What is the PARP inhibitor resistance problem?
Resistance to PARP inhibitors typically involves restoration of HRR functionality: reversion mutations in BRCA1/2 (that restore the reading frame), BRCA1 promoter demethylation, upregulation of alternative repair pathways (NHEJ via 53BP1 loss), or increased drug efflux. Secondary resistance emerges in virtually all patients on continuous PARP inhibitor therapy. Second-line strategies — sequential PARPi, PARP+IO, PARP+WEE1 inhibitor combinations — are being tested in multiple Phase 2 trials.
What are the key monitoring keywords for PARP inhibitor competitive intelligence?
The most productive ClinicalTrials.gov search terms for comprehensive PARP inhibitor coverage: "PARP inhibitor", "olaparib", "niraparib", "talazoparib", "rucaparib", "veliparib", "pamiparib" (China), "fuzuloparib" (China), "HRD", "BRCA maintenance". DataLookout monitors all variants daily — no manual search required.