Table 3.

Summary of Phase II/III Clinical Trials of PARP Inhibitors

Clinical trial identifier	Treatment Arms	Phase	Status	Locations	Time	Study population and numbers	Treatment	Median Follow-up Duration	Outcomes	Adverse Effects
Breast cancer
NCT02000622 (OlympiAD)	Olaparib vs. physician’s choice of Capecitabine, Vinorelbine or Eribulin	III	Completed	19 countries	2014–2016	BRCA-mutant, HER2 negative metastatic breast cancer ( N = 302)	Patients were administered olaparib orally twice daily (bid) at 300 mg.		Median PFS was significantly longer in the olaparib group than in the standard therapy group (7.0 vs. 4.2 mo). The response rate was 59.9% in the olaparib group vs. 28.8% in the standard therapy group.	The grade 3 or higher AE rate was 36.6% in olaparib group vs. 50.5% in the standard-therapy group. The rate of treatment discontinuation was 4.9% and 7.7%, respectively.
NCT01945775 (EMBRACA)	Talazoparib vs. physician’s choice of Capecitabine, Eribulin, Gemcitabine or Vinorelbine	III	Completed	United States	2013–2017	Breast neoplasms, HER2 negative, BRCA mutations (N = 431)	Patient were randomized 2:1 to receive talazoparib oral capsules (1.0 mg) once daily for 21 continuous days.	Until 2018	Median PFS: 8.6 mo vs. 5.6 mo, HzR 0.54, 0.41 to 0.71, P < 0.001; The ORR: 62.2% vs. 27.2%, OR 5.0, 2.9–8.8, P < 0.01; Overall improvement was seen for talazoparib compared to PCT group (3.0, 1.2 to 4.8 vs. (−5.4), (−8.8 to −2.0), P < 0.0001. Greater delay was observed in definitive clinically meaning full deterioration (TTD) favoring talazoparib vs. PCT (HzR, 0.38, 2.26 to 0.55); median 24.3 mo vs. 6.3 mo, P < 0.0001	Hematologic grade 3–4 AE: 55% of the patients received talazoparib vs. 38% of the patients received standard therapy; nonhematologic grade 3 AE occurred: 32% vs. 38%, respectively.
NCT03575065	Pamiparib/BGB-290	II	Completed	China	2018–2021	Metastatic HER2 negative, BRCA-mutant breast cancer; TNBC cohort (N = 62); HR+/HER2- cohort (N = 26)	Patents received pamiparib 60 mg orally twice daily in 28-day cycles		In the TNBC cohort: confirmed ORR = 38.2% (95% CI: 25.4–52.3); median DOR = 6.97 months; median PFS = 5.49 months (95% CI: 3.65–7.33); median OS = 17.08 months (95% CI:13.70–NE). In the HR+ cohort: confirmed ORR = 61.9% (95% CI: 38.4–81.9); mDOR = 7.49 months (95% CI: 5.55–14.75); mPFS = 9.20 months (95% CI: 7.39–11.93); mOS was not reached	Grade 3 TEAEs occurred in 54 pts (61.4%); anemia was the most common TEAE, occurring in 77 pts (87.5%). Dose reduction due to TEAEs occurred for 57 pts (64.8%); discontinuation due to TEAEs occurred for 2 pts (2.3%)
NCT02032823 (OlympiA)	Olaparib vs. Placebo	III	Ongoing	23 countries	2014-current	gBRCA1/2 mutations and high risk HER2 negative primary breast cancer (N = 1836)	Olaparib tablets 300mg b.i.d. p.o.		Adjuvant olaparib after completion of local treatment and neoadjuvant/adjuvant chemotherapy significantly increased survival free of invasive or distant disease than was placebo.	Most common reasons for discontinuation of olaparib: nausea (2.0%), anemia (1.8%), fatigue (1.3%), and decreased neutrophil count (1.0%).
NCT01905592 (BRAVO)	Niraparib vs. physician’s choice of single-agent chemotherapy	III	Ongoing	United States	2014-current	Neoplasms, breast and BRCA mutant, HER2 negative (N = 306)	300 mg (3×100 mg capsules) once daily until progression or unacceptable toxicity develops		The hypothesis of median PFS improvement is 3 versus 6 months for physician’s choice and niraparib, respectively, with a hazard ratio of 0.5 and power of 99.6% for the primary PFS analysis.
Ovarian Cancer
NCT01844986 (SOLO1)	Olaparib vs. Placebo	III	Ongoing	15 countries	2013-current	Patients with BRCA mutated, newly diagnosed advanced high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer following first-line platinum-based chemotherapy (N = 457)	Olaparib tablets p.o. 300mg twice daily	41 mo	The risk of disease progression or death was 70% lower with olaparib than with placebo. Mean quality-adjusted PFS: olaparib 29.75 vs placebo 17.58 months, P < 0.0001; mean duration of time without significant symptoms of toxicity (olaparib 33.15 vs placebo 20.24 months, P < 0.0001).	Consistent with the known toxic effects of olaparib
NCT01874353 (SOLO2/ENGOT-Ov21)	Olaparib vs. Placebo	III	Ongoing	16 countries	2013-current	Platinum sensitive, BRCA mutated relapsed ovarian cancer (N = 327)	Olaparib 300mg in two 150 mg tablets twice daily		Median OS: 51.7 mo with olaparib vs. 38.8 mo with placebo	Anemia (21%) was the most common adverse effect. 26% of patients reported severe treatment-emergent adverse effects with olaparib versus 8% with placebo. Fatal outcomes occurred in 4% of patients with olaparib attributed to myelodysplastic syndrome (n = 3) and acute myeloid leukemia (n = 3).
NCT02477644 (PAOLA-1)	(1) Bevacizumab + Olaparib (p.o. 300 mg bid) vs. Bevacizumab + Placebo; (2) Olaparib vs. Placebo	III	Ongoing	11 countries	2015-current	Advanced FIGO Stage IIIB-IV high grade serious or endometrioid ovarian, fallopian tube, or peritoneal cancer treated standard first-line treatment	Tablets, per os, 300 mg twice daily	22.9 mo	Median PFS: (1) 22.1 mo vx. 16.6 mo; HzR, 0.59: (0.49 to 0.72); P<0.001; (2) 37.2 mo vs. 17.7 mo; HzR, 0.33; (0.25 to 0.45) in patients with HRD including BRCA-mutation; 28.1 mo vs. 16.6 mo; HzR, 0.43; (0.28 to 0.66) in patients with HRD without BRCA mutations
NCT02282020. (SOLO3)	Olaparib vs. physician’s choice of single agent chemotherapy	III	Ongoing	United States	2015-current	gBRCA-mutant platinum-sensitive relapsed ovarian cancer (N = 266)	Olaparib 300mg oral tablets; twice daily or single-agent nonplatinum chemotherapy (paclitaxel, gemcitabine, pegylated liposomal doxorubicin, or topotecan).		ORR was significantly higher with olaparib than with chemotherapy (72.2% vs. 51.4%). BICR-assessed PFS also significantly favored olaparib vs. chemotherapy (13.4 mo vs. 9.2 mo).	Consistent with the established safety profiles of olaparib and chemotherapy.
NCT03402841 (OPINION)	Olaparib maintenance monotherapy	IIIb	Ongoing	17 countries	2018-current	Non-germline BRCA mutated ovarian cancer (N = 279)	300 mg twice daily - oral until disease progression or unacceptable toxicity.	Until Oct 2020 (75.3% data maturity)	Median PFS was 9.2 months. PF at 6, 12 and 18 months were 65.3%, 38.5% and 24.3%, respectively. A grade higher than 3 treatment-emergent AEs occurred in 29% of patients and serious TEAEs in 19.7% of patients.	Consistent with the known toxic effects of olaparib
NCT02476968 (ORZARA)	Olaparib maintenance monotherapy	IV	Ongoing	8 countries	2015–2021	Platinum sensitive relapsed somatic or germline BRCA mutated ovarian cancer patients with the complete or partial response following platinum-based chemotherapy (N = 181)	Olaparib capsules orally 400 mg twice daily within 8 weeks after their last dose of platinum-containing chemotherapy until disease progression or discontinuation.	Until April 2020 (60% data maturity)	In the BRCA-mutant cohort, the median PFS was 18.9 months, and the PFS rate was 67% at 1 year and 30% at 2 years. In patients with non-BRCA HRR mutations, the median PFS was 16.4 months and the PFS rate at 1 and 2 years were 68% and 26%, respectively. Treatment-emergent AEs of any grade, a grade higher than 3, and serious events were 93%, 38.2%, and 23.6, respectively, among all BRCA-mutant patients.	The most common AEs of any grade included nausea (53.7%), fatigue (53.7%), anemia (42.4%), and vomiting (27.7%)
NCT01891344 (ARIEL2)	Rucaparib	II	Completed	7 countries	2013–2019	Part I (N = 204) and Part II (N = 287): patients with recurrent, platinum-sensitive, HGSOC were classified into one of three predefined HRD subgroups: BRCA mutant, BRCA WT and LOH high (LOH high group), or BRCA WT and LOH low (LOH low group).	600 mg twice per day for continuous 28-day cycles until disease progression or any other reason for discontinuation	Between Oct 2013 and Aug 2016, 491 patients were enrolled.	Part I: median PFS: 12.8 mo, (9.0–14.7) in BRCA mutant group vs. 5.7 (5.3–7.6) in LOH high group vs/ 5.2 (3.6–5.5) in LOH low group. PFS is significantly longer in BRCA mutant (HzR 0.27, 0.16–0.44, P < 0.0001) and LOH high (HzR 0.62, 0.42–0.9, P = 0.011) compared to LOH low group. Part II: confirmed ORR: 31% (21.3–42), 6.8% (2.3–15.3) and 5.6% (2.1–11.8), respectively. Median PFS: 7.8 mo (7.3–9.2) vs 4.3 mo (3.5–5.7) vs 4.0 mo (3.5–5.3), P < 0.001)	The most common grade 3 or worse AE were anemia or decreased hemoglobin (22% patients), followed by elevated ALT or AST (12%). Common serious AE included small intestine obstruction (5%), malignant neoplasm progression (5%). No treatment-related deaths occurred.
NCT01968213 (ARIEL3)	Rucaparib vs. Placebo	III	Completed	11 countries	2014–2016	Platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma (N = 564)	Randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28-day cycles using a computer-generated sequence	Between April 7, 2014, and July 19, 2016	Median PFS in BRCA-mutant carcinoma was 16.6 months in the rucaparib group vs. 5.4 months in the placebo group. In patients with a HR deficient carcinoma, it was 13.6 vs. 5.4 months respectively.	TEAE of grade 3 or higher were reported in 56% of patients in the rucaparib group and 15% in the placebo group. The most common AEs included anemia or decreased hemoglobin concentration (19% vs 1%) and increased alanine or aspartate aminotransferase concentration (10% vs. none).
NCT01847274 (ENGOT-OV16/NOVA Study)	Niraparib	III	Ongoing	GSK, US	2013-current	Patients with platinum sensitive ovarian cancer (N = 578)	Niraparib vs placebo at 2:1 ratio administered once daily continuously during a 28-day cycle.
NCT02354586 (QUARA)	Niraparib	II	Completed	US, Canada		Ovarian Cancer Who Have Received Three or Four Previous Chemotherapy Regimens		Between April 1, 2015 to Nov 1, 2017	Median OS = 12.2 months	Small intestinal obstruction, thrombocytopenia, vomiting
NCT02655016 (PRIMA)	Niraparib	III	Ongoing		2016-current	Maintenance Treatment in Participants with Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy			Median PFS in patients treated with niraparib vs. placebo = 21.9 vs 10.4 months (HR = 0.43, 0.31–0.59) and OS = 13.8 vs. 8.2 months, respectively.	Anemia, thrombocytopenia and neutropenia
NCT03519230	Pamiparib/BGB-290	III	Ongoing	China	2018-current	Platinum-sensitive recurrent ovarian cancer (N = 216)
NCT01540565	Veliparib/ABT-888	II	Completed	United States	2012–2018	Persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (N = 52)	Veliparib orally twice daily on days 1–28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NCT02470585 (VELIA)	Veliparib plus Carboplatin and Paclitaxel	III/IV	Ongoing	United States	2015-current	Patients with newly diagnosed stage III or IV, high-grade serous, epithelial ovarian, fallopian tube, or primary peritoneal cancer (N = 1140)	Placebo + Carboplatin + Paclitaxel (C/P) -> Placebo; Veliparib + C/P -> Placebo; Veliparib + C/P -> Veliparib. Veliparib: 150 mg orally. Paclitaxel: intravenous infusion, either 80 mg/m2 of body-surface area (BSA) on Days 1, 8, and 15 of each 21-day cycle (weekly dosing), or 175 mg/m2 of BSA on Day 1 of each 21-day cycle (3-week dosing). Carboplatin: intravenous infusion at an area under the curve (AUC) of 6 mg/mL/min every 3 weeks.		In the BRCA-mutation cohort, the median PFS = 34.7 (veliparib) vs. 22 (control), HR = 0.44, 0.28–0.68. In the HRD cohort, the median PFS = 31.9 vs. 20.5 respectively, HR = 0.57, 95% CI: 0.43–0.76	Anemia, thrombocytopenia, nausea, and fatigue
Prostate Cancer
NCT02987543 (PROfound Study)	Olaparib vs. physician’s choice of enzalutamide or abiraterone plus prednisone	III	Ongoing	21 countries	2017-current	Metastatic castration-resistant prostate cancer who have failed prior treatment with a new hormonal agent and have HR repair gene mutations	300 mg (2× 150 mg tablets) twice daily; enzalutamide (160 mg once daily) or abiraterone (1000 mg once daily) plus prednisone (5 mg twice daily)	Analysis data cutoff date of June 4, 2019	Median PFS: Cohort A (at least one alteration in BRCA1, BRCA2, or ATM): 19.1 mo vs. 14.7 mo; HzR, 0.69; (0.50 to 0.97); P<0.02; Cohort B (at least one alteration in any of the other 12 prespecified genes): 14.1 mo vs. 11.5 mo
NCT02952534 (TRITON2)	Rucaparib	II	Completed	12 countries	2016–2021	Metastatic castration-resistant prostate cancer a BRCA alteration (N = 115)	Rucaparib 600 mg twice daily		Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. ORRs were similar for patients with a germline or somatic BRCA alteration and patients with a BRCA1 or BRCA2 alteration.	The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients).
Pancreatic Cancer
NCT02184195 (POLO)	Olaparib vs. Placebo	III	Completed	United States	2014–2019	Patients with gBRCA mutated metastatic pancreatic cancer without progression on first-line platinum-based chemotherapy (N = 154)	Olaparib tablets po. 300 mg twice daily		Median PFS was significantly longer in the olaparib group than in the placebo group (7.4 vs. 3.8 mo).	The incidence of grade 3 or higher AE was 40% in the olaparib group and 23% in the placebo group.
Gastric Cancer
NCT03427814	Pamiparib/BGB-290	III	Ongoing	United States	2018-current	Metastatic gastric cancer (N = 136)

HRD, homologous recombination deficiency; HGSOC, high-grade serous ovarian carcinoma; LOH, loss of heterozygosity; HRR, homologous recombination repair; PFS, progression-free survival; ORR, objective response rate; DOR, duration of response; OS, overall survival; PCT, physician’s choice of chemotherapy; AE, adverse event; TEAE, treatment-emergent adverse event; HzR/HR, hazard ratio; CI, confidence interval; BID/b.i.d., twice a day; p.o., per os/oral; mo, month