Table 2.

Sumary of completed phase 1 trials involving patients with pancreatic cancer

PARPi	Author	Design	N (N Pancreas)	Tumor types included	Mutations (n with mutations)	Key Findings	Ref
Olaparib	Fong	Phase 1 dose escalation with expansion phase of only patients with BRCA mutations	60 (2)	Advanced solid tumors refractory to established therapies (ovarian, breast, colorectal, melanoma, sarcoma, prostate, other)	Not required in the initial cohort, expansion cohort enrolled only patients with BRCA1/2 mutations (n=22)	MTD 400 mg BID Sufficient inhibition of PARP achieved at olaparib 60 mg BID Fatigue and nausea were common side effects. 9 of 19 evaluable patients with BRCA mutations had a response	36
Rucaparib	Plummer	Phase 1 dose escalation in combination with temozolomide 100 mg/m2 escalating to 200 mg/m2 daily days 1–5 of 28 day cycles	32 (1)	Advanced solid tumors (sarcoma, melanoma, colorectal, other)	Not reported	RP2D: rucaparib 12 mg/m2 and temozolomide 200 mg/m2 days 1–5 of 28 day cycles. Grade 3 neutropenia occurred in high doses One patient with pancreatic cancer experienced prolonged disease stabilization	40
	Kristeleit	Phase 1 3+3 dose escalation	56 (2)	Ovarian cancer and other solid tumors	All patients had germline BRCA1/2 mutations	RP2D: 600 mg BID Fatigue, myelosuppression. Gastrointestinal upset were common but manageable. One of the two patients with pancreatic cancer experienced a prolonged response	30
Niraparib	Sandhu	Phase 1 dose escalation	100 (1)	Advanced solid tumors	With (29) or without BRCA mutations	MTD and RP2D: 300 mg/day Anemia, thrombocytopenia, neutropenia, fatigue were common. Single patient with pancreatic cancer possessed BRCA2 mutation and did not respond to treatment	37
Veliparib	O’Reilly	Single arm phase 1 dose escalation study with gemcitabine 600 mg/m2 day 3 and 10 and cisplatin 25 mg/m2 days 3 and 10	17 (17)	Advanced or metastatic pancreatic cancer and were naïve to platinum-based therapies	BRCA mutations (9) or family history of BRCA-related cancers	RP2D: 80 mg BID 11ay 1–12 of 21 day cycles in combination with cisplatin and gemcitabine Grade 4 neutropenia and thrombocytopenia were common Objective responses only seen in patients with BRCA mutations (7 of 9 patients) One patient developed acute myeloid leukemia 2.5 years into therapy	42
	Tuli	Single arm phase 1 combining veliparib with gemcitabine and radiation	30 (30)	Treatment-naïve locally advanced pancreatic cancer or borderline resectable pancreatic cancer	No patient had BRCA1 or BRCA2 mutations Nine patients with mutations in other DNA damage repair genes (ARID1A, ATM, CHECK2, PALB2, PTEN, and loss of MLH1).	MTD: 40 mg BID Lymphopenia and Anemia were common Grade 3 Aes Slightly longer median OS in patients with mutations in DDR	43
Talazoparib	de Bono	Dose escalation followed by expansion cohort	113 (13)	Tumors predicted to be potentially sensitive to PARPi, including germline BRCA1/2 mutations	With (59) or without germline BRCA mutations	4.0 mg/day RP2D Marrow toxicity common 2/13 pancreatic cancer patients had a PR (one with BRCA2 mutation, one with PALB2 mutation)	39
Fluzoparib	Li	Phase 1 3+3 dose escalation	79 (2)	Advanced solid tumors	With (59) or without BRCA mutations	MTD: 150 mg BID Antitumor responses seen in platinum resistant and platinum-refractory BRCA mutated cancers	38

RP2D: Recommended phase 2 dose, MTD: Maximum tolerated dose, BID: twice daily, AE: adverse event DDR: DNA Damage Repair, PR: partial response.