Table 3.
PARP inhibitor plus immune checkpoint blockade clinical trials.
| Trial Name/NCT Number | Phase | Drugs | Eligible Patients | Dose/Schedule | Findings of Primary Endpoint(s) | Findings of Secondary Endpoint(s) | Notable common grade AEs (≥10%) |
|---|---|---|---|---|---|---|---|
| Completed PARPi plus ICB trials | |||||||
| TOPACIO/KEYNOTE-162 NCT02657889 Konstantinopoulos PA, et al. JAMA Oncology (2019). |
Open-label, single-arm phase I/II | Niraparib plus pembrolizumab (pembro) | Advanced recurrent or metastatic TNBC (n = 5 (phase I)) or ovarian carcinoma (n = 9 (phase I), n = 53 (phase II)) | Niraparib 200–300 mg (phase I) or 200 mg (phase II) PO QD plus pembro 200 mg IV q3w |
RP2D (phase I): niraparib 200 mg PO QD plus pembro 200 mg IVq3w ORR (phase II): 18% (11–29) among ovarian carcinoma (n = 62) pts across phases I & II |
DCR (CR + PR + SD): 65% (54–75) PFS: 3.4 mo (2.1–5.1) |
Anemia (36%), thrombocytopenia (36%), neutropenia (14%) in phase I Anemia (21%) in phase II |
| Ongoing/incomplete PARPi plus ICB trials | |||||||
| FIRST/ENGOT-ov44 NCT03602859 Hardy-Bessard AC, et al. Journal of Clinical Oncology (2019). Abstract. |
Randomized, double-blind phase III | SOC plus dostarlimab first line treatment, then maintenance bevacizumab, niraparib, and dostarlimab | Advanced nonmucinous epithelial ovarian cancer | SOC (paclitaxel 175 mg/m2, AUC 5–6 mg/mL/min q3w, bevacizumab 7.5–15 mg/kg q3w) for 1 cycle, then SOC plus dostarlimab (arm 3) vs. placebo (arms 1, 2) 1000 mg q6w for 5 cycles Maintenance with bevacizumab 7.5–16 mg/kg q3w plus niraparib (arms 2, 3)/placebo (arm 1) 100 mg PO plus dostarlimab (arm 3) vs. placebo (arms 1, 2) 1000 mg q6w |
PFS (all participants) PFS (PD-L1 positive tumors) |
PFS (per BICR), OS, safety & tolerability, pharmacokinetics, quality of life (EORTC-QLQ), TFST, PFS2, ORR, duration of response, DCR | No published data |
| ATHENA NCT03522246 |
Randomized, double-blind phase III | Maintenance rucaparib plus nivolumab (nivo) | Newly diagnosed advanced epithelial ovarian, fallopian tube, or peritoneal cancer with investigator-assessed response to first-line platinum treatment | Maintenance rucaparib PO plus nivo IV (arm A) vs. plus placebo IV (arm B) vs. maintenance placebo PO plus nivo IV (arm C) vs. plus placebo IV (arm D) | PFS | PFS (per BICR), OS, ORR, duration of response, safety & tolerability | No published data |
| JAVELIN OVARIAN PARP 100 NCT03642132 Eskander RN, et al. Journal of Clinical Oncology (2019). Abstract. |
Randomized, open-label phase III | Platinum-based chemotherapy plus avelumab, then maintenance avelumab plus talazoparib | Treatment-naïve, advanced/metastatic epithelial ovarian, fallopian tube, or primaty peritoneal cancer | Chemotherapy (paclitaxel 175 mg/m2, carboplatin AUC 5–6 IV q3w) plus concurrent avelumab 800 mg IV q3w followed by avelumab plus talazoparib (arm A) vs. Chemotherapy followed by talazoparib maintenance 0.75 mg PO QD (arm B) vs. Chemotherapy pus concurrent bevacizumab followed by bevacizumab 15 mg/kg IV q3w maintenance (arm C) | PFS (per BICR) | OS, PFS2, quality of life (EQ-5D-5L) | No published data |
| ENGOT-ov43/KEYLYNK-001 NCT03740165 Vergote I, et al. Journal of Clinical Oncology (2019). Abstract. |
Randomized, double-blind phase III | Chemotherapy plus pembrolizumab (pembro), then maintenance olaparib | Advanced, non-BRCA mutated epithelial ovarian, fallopian tube, or primary peritoneal cancer | Chemotherapy (carboplatin plus paclitaxel IV) for 5 cycles plus concurrent pembro followed by pembro plus olaparib maintenance (arm 1) for up to 35 cycles vs. Chemotherapy plus concurrent pembro followed by pembo plus placebo maintenance (arm 2) for up to 35 cycles Chemotherapy (arm 3) |
PFS OS |
PFS (per BICR), PFS2, safety & tolerability, quality of life (EORTC-QLQ-c30), TFST | No published data |
|
NCT02571725 Adams SF, et al. Journal of Clinical Oncology (2017). Abstract. |
Open-label phase I/II | Olaparib plus tremelimumab (treme) | Recurrent epithelial ovarian, fallopian tube, or primary periteonal carcinoma with gBRCA1/2m (n = 3 (phase I)) | Olaparib 300 mg PO BID plus treme 10 mg/kg (reduced to 3 mg/kg minimum if sufficient DLT) (phase I) or at RP2D (phase II) IV q4w for first 6 interventions, then q12w | RP2D (phase I): olaparib 300 mg PO BID plus treme10 mg/kg IV q4w ORR (phase II) |
PFS (phase II | No published data |
| NCT04034927 | Randomized, open-label phase II | Olaparib plus tremelimumb (treme) vs. Olaparib alone | Platinum-sensitive, high-grade serious or endometrioid ovarian, fallopian tube, or primary peritoneal cancer | Olaparib plus treme q4w for first 4 interventions, then q12w vs. Olaparib | PFS Dose-limiting toxicities RECISTv1.1 response | ORR, OS, AE | No published data |
| MEDIOLA NCT02734004 Drew Y, et al. Annals of Oncology (2020). Abstract. |
Open-label phase I/II | Olaparib plus durvalumab (durva) | Platinum-sensitive recurrent gBRCAm or non-gBRCAm ovarian cancer | Olaparib 300 mg PO BID plus durva 1.5 g IV q4w (phase II) | 24-wk disease control rate: 28.1% (90% CI 15.5–43.9) Safety& tolerability | ORR: 31.3% (16.1–50.0) Median duration of response: 6.9 mo (IQR 5.7–11.1) Median PFS: 5.5 mo (3.6–7.5) |
No published data |
| GUIDE2REPAIR NCT04169841 Fumet JD, et al. BMC Cancer (2020). |
Open-label phase I/II | Olaparib plus durvalumab (durva) plus tremelimumab (treme) | Platinum-sensitive HRD + ovarian cancer | Olaparib 300 mg PO BID for 8 weeks, then olaparib 300 mg PO BID plus durva 1500 mg IV q4w plus treme 75 kg IV q4w for up to 4 doses, then durva 1.5 g IV q4w | 12-week PFS from 1st dose of ICB | 12-week DCR, OS, ORR, toxicity | No published data |
| NCT02953457 | Open-label phase I/II | Olaparib plus durvalumab (durva) plus tremelimumab (treme) | Platinum-sensitive/resistant/refractory recurrent HRD + or somatic/gBRCAm epithelial ovarian, fallopian tube, or primary peritoneal cancer | Olaparib PO BID up to 12 months plus durva IV q3w up to 13 courses plus treme IV q4w up to 4 courses | Dose-limiting toxicities (phase I) PFS (platinum-resistant group) PFS (platinum-sensitive group) |
OS, biomarker analyses | No published data |
| NCT02484404 | Open-label phase I/II | Olaparib plus durvalumab (durva) | Previously treated (≥2 lines) or platinum-resistant/refractory recurrent ovarian, fallopian tube, or primary peritoneal cancer (phase II) | Olaparib 200–300 mg PO BID plus durva 3–10 mg/kg IV q2w OR 10 mg/kg IV q4w (phase I), RP2D olaparib plus durva (phase II) |
RP2D (phase I) Safety and tolerability ORR | ORR, median duration of response, PK parameters (phase I) PFS, safety, biomarker analysis (phase II) | No published data |
*
All reported ranges are 95% CI unless otherwise stated
Abbreviations: AE: adverse event; BICR: blinded independent central review; BID: twice daily; CR: complete response; DCR: disease control rate; DLT: dose-limiting toxicity; EORTC QLQ-c30: European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30; ICB: immune checkpoint blockade; IQR: interquartile range; ORR: objective response rate; OS: overall survival; PARPi: poly (ADP-ribose) polymerase inhibitor; PFS2: second progression-free survival; PFS: progression-free survival; PO: by mouth; PR: partial response; QD: once daily; RECIST: response evaluation criteria in solid tumors; RP2D: recommended phase 2 dose; SD: stable disease; SOC: standard of care; TFST: time to first subsequent therapy; mo: months; q2w: once every 2 weeks; q3w: once every 3 weeks; q4w: once every 4 weeks; HRD: homologous recombination deficiency; gBRCAm: germline BRCA mutated; gBRCA1/2m: germline BRCA1/2 mutated.