Table 4.
Ongoing clinical trials of poly(ADP‐ribose) polymerase inhibitors
| Drug and trial no. | Status | Phase | Treatment | Patient population | Primary endpoint | Biomarkers included in eligibility criteria |
|---|---|---|---|---|---|---|
| Olaparib | ||||||
| NCT03434158 (IMANOL) | Active | II | Olaparib, maintenance | Patients with mCRPC after docetaxel treatment reaching partial or stable response | Progression‐free survival | BRCA1, BRCA2, ATM, FANC genes, CHEK2, MLH1, MSH2, MSH6, PMS2, PALB2, RAD51C, MRE11 |
| NCT03432897 | Active | II | Olaparib, neoadjuvant | Patients with locally advanced Pca and defects in DNA repair genes | PSA response rate | BRCA1, BRCA 2, ATM, CHEK1, CHEK2, FANCONIS ANEMIA (FANCL), HDAC2, PALB2, BARD1, BRIP1, CDK12, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L |
| NCT03810105 | Active | II | Olaparib + durvalumab | Patients with castration sensitive, biochemically recurrent, nonmetastatic PCa and DDR mutations | Undetectable PSA | BRCA1, BRCA2, ATM, CHEK2, FANCA, RAD51C, RAD51D, PALB2, BRIP1, BARD1, or CDK12 |
| NCT03012321 | Active | II | Abiraterone/prednisone, olaparib vs. abiraterone/prednisone + olaparib | Patients with mCRPC and DDR defects | Objective progression‐free survival | ATM, BRCA1, BRCA2, FANCA, PALB2, RAD51, ERCC3, MRE11, NBN, MLH3, CDK12, CHEK2, HDAC2, ATR, PMS2, GEN1, MSH2, MSH6, BRIP1, FAM175A |
| NCT03570476 | Suspended (COVID‐19) | II | Olaparib, neoadjuvant | Patients with localized PCa and DNA repair deficiencies | Pathological complete response rate | BRCA1, BRCA2, ATM, PALB2 (germline) or BRCA1, BRCA2, PALB2, FANCA, ATM (somatic) |
| NCT02987543 (PROfound) | Active, not recruiting | III | Olaparib vs. enzalutamide or abiraterone | Patients with mCRPC who have failed prior treatment with a new hormonal agent and have qualifying tumor mutation in an HR gene | Radiographic progression‐free survival | BRCA1, BRCA2, ATM, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L |
| NCT03516812 | Active, not yet recruiting | II | Olaparib + durvalumab | Nonmetastatic patients predicted to have a high neoantigen load that have received local therapy | Undetectable PSA | CDK12, mismatch repair deficiencies, or HR repair deficiencies |
| NCT03263650 | Active | II | Olaparib following cabazitaxel | Patients with aggressive variant Pca | Progression‐free survival | None |
| NCT03317392 | Active | I/II | Olaparib + radium 223 | Patients with mCRPC that has spread to the bone | Maximum tolerated dose, progression‐free survival | None |
| NCT03787680 (TRAP) | Active | II | Olaparib + AZD6738 | Patients with mCRPC with or without DDR mutations | Complete or partial response in DNA repair proficient patients | General DNA repair deficiency |
| NCT03047135 | Active | II | Olaparib only | Patients with high‐risk biochemically recurrent PCa following radical prostatectomy | PSA repsonse rate | None |
| NCT02893917 | Active, not recruiting | II | Olaparib with or without cediranib | Patients with mCRPC | Progression‐free survival | None |
| NCT03732820 (PROpel) | Active | II | Olaparib + abiraterone vs. placebo + abiraterone | Patients with mCRPC who have received no prior cytotoxic chemotherapy or new hormonal agents | Radiological progression‐free survival | None |
| NCT01972217 | Active, not recruiting | II | Olaparib + abiraterone vs. placebo + abiraterone | Patients with mCRPC |
Part A: adverse events, dose limiting toxicities; part B: radiological progression‐free survival, progression or death |
None |
| Rucaparib | ||||||
| NCT03413995 (TRIUMPH) | Active | II | Rucaparib only | Patients with mCRPC who have not yet been treated with ADT and germline mutations in DNA damage genes | PSA response rate | BRCA1, BRCA2, ATM, CHEK2, NBN, RAD50, RAD51C, RAD51D, PALB2, MRE11, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM |
| NCT03442556 | Active | II | Carboplatin and docetaxel followed by maintenance rucaparib | Patients with mCRPC and HR repair deficiency | Radiographic progression‐free survival | ATM, BRCA1, BRCA2 |
| NCT03533946 (ROAR) | Active | II | Rucaparib only | Patients with castration sensitive PCa demonstrating "BRCAness" | PSA response rate | ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, ERCC3, FAM175A, FANCA, FANCL, GEN1, HDAC2, MLH1, MRE11, NBN, PALB2, PPP2R2A, RAD51, RAD54L |
| NCT04253262 | Active | I/II | Rucaparib + copanlisib | Patients with mCRPC | Phase I: maximum tolerated dose; phase II: overall response | Phase I: none; phase II: BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, FANCL, FANCA, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L |
|
(LODESTAR) |
Active | II | Rucaparib only | Patients with various solid tumors and with deleterious mutations in HRR genes | Best overall response rate | BRCA1, BRCA2, PALB2, RAD51C, RAD51D, BARD1, BRIP1, FANCA, NBN, RAD51, RAD51B |
|
(TRITON2) |
Active, not recruiting | II | Rucaparib only | Patients with metastatic castration‐resistant prostate cancer, and evidence of a homologous recombination gene deficiency | Objective response rate, prostate specific antigen response | ATM, BRCA1, BRCA2, BARD1, BRIP1, CDK12, CHEK2, FANCA, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D, RAD54L, or other |
|
(TRITON3) |
Active | III | Rucaparib vs. abiraterone or enzalutamide | Patients with mCRPC and evidence of a homologous recombination gene deficiency | Radiographic progression‐free survival | ATM, BRCA1, BRCA2, or other HR gene mutation |
| Talazoparib | ||||||
| NCT03330405 | Active, not recruiting | II | Avelumab + talazoparib | Patients with mCRPC | Dose limiting toxicity, Overall response | ATM, BRCA1, BRCA2 |
| NCT03148795 (TALAPRO) | Active, not recruiting | II | Talazoparib only | Patients with mCRPC and DNA repair defects who have previously received taxane‐based chemotherapy and have progressed on at least 1 hormonal agent | Objective response rate | General DNA repair deficiency |
| NCT03395197 (TALAPRO2) | Active | III | Talazoparib + enzalutamide vs. placebo + enzalutamide | Patients with mCRPC | Dose confirmation, radiographic progression‐free survival | None |
| NCT04332744 | Active, not yet recruiting | II | Talazoparib + enzalutamide | Patients with metastatic, castration‐sensitive PCa | PSA response rate | None |
| Niraparib | ||||||
| NCT04030559 | Active | II | Niraparib: neoadjuvant | Patients with localized PCa and alterations in DNA repair pathways | Pathologic complete response | ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCA, FANCD2, FANCL, GEN1, NBN, RAD51, RAD51C, and other DDR genes |
| NCT04288687 | Active, Not yet recruiting | II | Niraparib only | Patients who have recently received platinum‐based therapy | Radiographic progression‐free survival | BRCA1/2, ATM, FANCA, PALB2, CHEK2, HDAC2, or BRIP1 |
| NCT02854436 (GALAHAD) | Active | II | Niraparib only | Patients with mCRPC and DNA repair anomalies | Objective response rate | BRCA1, BRCA2, and other DDR genes |
| NCT04037254 | Active | II | Niraparib + ADT | Patients with PCa with a high chance of recurrence | Preferred dose, PSA response | None |
| NCT03748641 | Active | III | Niraparib + abiraterone vs. placebo + abiraterone | Patients with mCRPC | Progression‐free survival | None |
| Other | ||||||
| NCT04182516 | Active | I | NMS‐03305293 | Patients with selected advanced or metastatic, relapsed, or refractory solid tumors who have exhausted standard treatment options or for whom standard therapy is considered unsuitable | First‐cycle dose limiting toxicity | BRCA1, BRCA2 |
Abbreviations: DDR, DNA damage repair; HR, homologous recombination; HRR, homologous recombination repair, mCRPC, metastatic castration‐resistant prostate cancer; PCa, prostate cancer; PSA, prostate‐specific antigen.