Table 4.
Triplet combination (antiangiogenic therapy plus immune checkpoint blockade plus PARP inhibitor) 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 triplet combination trials | |||||||
|
NCT02484404 Zimmer AS, et al. J, Immunother. Cancer (2019). |
Open-label, dose-escalation phase I | Olaparib plus durvalumab (durva) plus cediramb | Advanced breast or gynecologic malignancies (n = 9) | Olaparib 200–300 mg PO BID plus durva 1.5 g IV q4w plus cediranib 15–20 mg PO QD (5 days on/2 days off) | RP2D: olaparib 300 mg PO BID plus durva 1.5 mg IV q4w plus cediranib 20 mg PO QD (5 days on/2 days off) | ORR: 44% Median duration of response: 8.5 mo (7–26) CBR (CR + PR + SD ≥ 6 mo): 67% | Lymphopenia (33%), anemia (22%) |
| Ongoing/incomplete triplet combination trials | |||||||
| AGO/DUO-O/ENGOT-ov46 NCT03737643 Harter P, et al. Journal of Clinical Oncology (2019). |
Randomized, double-blind phase III | Platinum-based chemotherapy plus durvalumab (durva) plus bevacizumab (bev), then maintenance bev (optional for tBRCAm cohort) plus durva plus olaparib | Newly diagnosed, advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer |
Non-tBRCAm cohort: Platinum based chemotherapy and bev IV plus placebo (arm 1) OR plus durva (arms 2, 3) Maintenance bev with double placebo IV (arm 1) vs. durva plus placebo (arm 2) vs. durval plus olaparib (arm 3) tBRCAm cohort: Platinum-based chemotherapy plus durva IV for 6 cycles Maintenance durva IV plus olaparib PO BID, with bev IV optional |
PFS | OS, ORR, duration of response | No published data |
| MEDIOLA NCT02734004 Drew Y, et al. Annals of Oncology (2020). Abstract. |
Open-label phase I/II | Olaparib plus durvalumab (durva) plus bevacizumab (bev) | Platinum-sensitive recurrent ovarian cancer with no BRCAm (n = 31) | Olaparib 300 mg PO BID plus durva 1.5 g IV q4w plus bev 10 mg/kg q2w | 24-week DCR: 77.4% (61.7–88.9) | ORR: 77.4% (58.9–90.4) Median duration of response: 11.1 mo(IQR 9.0–16.4) Median PFS: 14.7 mo (10.0–18.1) |
No published data |
| NCT02873962 | Open-label, single-arm phase II | Nivolumab (nivo) plus bevacizumab (bev) plus rucaparib | Platinum-sensitive or platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, with no germline or somatic deleterious BRCAm | Nivo IV q2w plus bev IV q2s plus rucaparib PO QD | ORR | PFS, ORR, duration of response, biomarker analysis | No published data |
*
All reported ranges are 95% CI unless otherwise stated
Abbreviations: AE: adverse event; BID: twice daily; CBR: clinical benefit rate; CR: complete response; DCR: disease control rate; IQR: interquartile range; ORR: objective response rate; OS: overall survival; PFS: progression-free survival; PO: by mouth; PR: partial response; QD: once daily; RP2D: recommended phase 2 dose; SD: stable disease; mo: months; q2w: once every 2 weeks; q3w: once every 3 weeks; q4w: once every 4 weeks; tBRCAm: tumor BRCA mutated; BRCAm: BRCA mutation