Table 2:
Novel Therapy Directions in DDR/HRD-Related Pancreas Cancer
| Drug | N | Cancer type | Phase | Design | Status | Reference |
|---|---|---|---|---|---|---|
| Niraparib | 32 | PDAC harboring deficiencies in HRR | 2 | Niraparib 200mg-300mg QD, palliative radiation therapy to a small field >1 week prior to day 1 of treatment | Recruiting | NCT03601923 |
| Niraparib | 18 | PDAC after previous chemotherapy | 2 | Niraparib 300mg daily for 28 days | Recruiting | NCT03553004 |
| Rucaparib | 220 | Solid tumors with HRR deleterious mutations | 2 | Rucaparib 600mg BID | Recruiting | NCT04171700 |
| Olaparib and pembrolizumab | 63 | Metastatic PDAC with HRR deficiency or exceptional treatment response to platinum | 2 | Arm A: Patients with mutations in core HR genes Arm B: Patients with mutations in non-core HR genes Arm C: Patients with previous PR/CR to platinum Pembrolizumab 200 mg Q3W. After the first 6 months (8 cycles), on C9D1 Pembrolizumab 400 mg Q6W. Olaparib 300 mg BID continuously (as a maintenance therapy). |
Recruiting | NCT04666740 |
| Dostarlimab and niraparib | 20 | gBRCA or somatic BRCA mutated pancreatic cancer | 2 | Niraparib QD on days 1–21. Dostarlimab on day 1 Q3W for cycles 1–4 and Q6W for subsequent cycles. Cycles repeat every 21 days for up to 2 years in the absence of POD or unacceptable toxicity | Recruiting | NCT04493060 |
| Niraparib and dostarlimab | 18 | BRCA mutated metastatic breast, pancreas, ovarian, fallopian tube, primary peritoneal. | 1 | Niraparib QD on days 1–28 of cycle 1. Cycle 2: patients receive niraparib QD on days 1–21 and dostarlimab on day 1. Repeats every 21 days for 4 cycles in the absence of POD or unacceptable toxicity. Beginning cycle 6, patients receive niraparib )D on days 1–42 and dostarlimab on day 1. Cycles repeat every 42 days for up to 24 months in the absence of POD or unacceptable toxicity | Not yet recruiting | NCT04673448 |
| Olaparib and pembrolizumab vs olaparib alone | 88 | Metastatic pancreatic cancer with gBRCA mutation SWOG S2001 |
2 | Arm A: Olaparib BID on days 1–21 and pembrolizumab IV on day 1. Repeats every 21 days for up to 18 cycles in the absence of POD or unacceptable toxicity. Cycle 19, patients receive Olaparib BID on days 1–42 and pembrolizumab day 1. Repeat every 42 days in the absence of POD or unacceptable toxicity. Arm B: olaparib BID on days 1–21. Cycles repeat every 21 days |
Recruiting | NCT04548752 |
| AZD6738 vs AZD6738 and olaparib | 68 | Solid tumors with ATM loss or ARID1A positivity in solid tumors | 2 | Arm A: BAF250a negative or ATM-Mutant receive AZD6738 PO twice a day on days 1–14. Treatment repeats every 28 days in the absence of POD or unacceptable toxicity. Arm B: BAF250a positive receive AZD6738 PO every day on days 1–7 and Olaparib twice a day on days 1–28. Treatment repeats every 28 days in the absence of disease POD or toxicity. |
Recruiting | NCT03682289 |
| Olaparib and durvalumab vs olaparib and durvalumab | 90 | Advanced solid tumors who have failed previous standard therapy | 2 | Arm A: Olaparib mg BID in combination with Durvalumab,1500 mg Q4W Arm B: Cediranib, 20 mg QD(5 days on 2 days off) in combination with Durvalumab 1500 mg Q4W. |
Recruiting | NCT03851614 |
| Niraparib and nivolumab and niraparib and ipilimumab | 84 | PDAC who have not progressed on platinum | 1/2 | Arm A: Niraparib 200mg QD on days 1–21 of each 21-day cycle. Nivolumab 240mg days 1 and 15 of odd-numbered cycles; day 8 of even numbered cycles Arm B: Niraparib 200mg QD on days 1–21 of each 21-day cycle Ipilimumab 3mg/kg day 1 of each cycle, for the first 4 cycles only |
Recruiting | NCT03404960 |
| Avelumab, binimetinib and talazoparib | 122 | RAS- mutant solid tumors | 1/2 | Arm A: Avelumab and binimetinib Arm B: Avelumab, binimetinib and talazoparib Arm C: Binimetinib and talazoparib |
Recruiting | NCT03637491 |
| Olaparib and cediranib | 126 | Advanced solid tumors | 2 | Cediranib maleate QD on day 1. Patients undergoing FMISO scan also receive Olaparib BID beginning the day after the second FMISO scan and the rest of the patients receive Olaparib BID beginning day 4 of cycle 1. Cycles repeat every 28 days (35 days for cycle 1) in the absence of POD or unacceptable toxicity | Recruiting | NCT02498613 |
| Olaparib and durvalumab vs cediranib and durvalumab | 90 | Advanced solid tumors | 2 | Arm A: Olaparib 300mg QD in combination with Durvalumab 1500 mg Q4W. Arm B: Cediranib20mg QD, 5 days on 2 days off in combination with Durvalumab 1500 mg Q4W |
Recruiting | NCT03851614 |
| Veliparib and dinaciclib | 118 | Advanced solid tumors | 1 | PART 1A: Veliparib BID on days 1–28 and dinaciclib, days 8 and 22. Cycles repeat every 28 days in the absence of POD or unacceptable toxicity PART 1B: Veliparib and dinaciclib as patients in Part 1A. PART 1C: Veliparib BID on days 1–7 of cycle 0. Veliparib BID on days 1–21 and dinaciclib on days 1, 4, 8, and 11 or days 1 and 8. Cycles repeat every 21 days in the absence of POD or unacceptable toxicity |
Recruiting | NCT01434316 |
| BAY1895344 usual chemotherapy | 54 | Advanced solid tumors | 1 | Gemcitabine on days 1 and 8, and BAY 1895344 BID on days 1–3 and 8–10. Cycles repeat every 21 days in the absence of POD or unacceptable toxicity | Not yet recruiting | NCT04616534 |
| BAY1895344 to usual chemotherapy | 87 | Advanced solid tumors, special focus on PDAC, SCLC, poorly differentiated neuroendocrine cancer. | 1 | Arm A: BAY 1895344 PO BID on days 1 and 2 and irinotecan liposome day 1. Cycles repeat every 14 days in the absence of POD or unacceptable toxicity. Arm B: Topotecan on days 1–5 and BAY 1895344 PO BID on days 2 and 5. Cycles repeat every 21 days in the absence of POD or unacceptable toxicity |
Not yet recruiting | NCT04514497 |
| AZD1775 and olaparib | 54 | Solid tumors who have PARP resistance | 1 | Olaparib BID on days 1–5 and 15–19 of each cycle and adavosertib PO QD on days 8–12 and 22–26 of each cycle. Cycles repeat every 28 days in the absence of POD or unacceptable toxicity | Recruiting | NCT04197713 |
| Copanlisib, olaparib and durvalumab | 102 | Solid tumors with mutations in HRR genes, PTEN, hotspot mutation in PIK3CA | 1 | Copanlisib hydrochloride on days 1, 8, and 15 and olaparib BID. Cycle 2, patients receive durvalumab on day 1. Cycles repeat every 28 days for 24 months in the absence POD or unacceptable toxicity | Recruiting | NCT03842228 |
QD: Once daily; BID: twice daily; HR: Homologous repair; PR: Partial response; CR: Complete response; QxW: Every x week; CxDy: Cycle x Day y; POD: Progression of disease; PO: orally.