Background: There are limited tx options for CIT. Epag, an oral, small molecule, thrombopoietin-receptor agonist that increases platelet (plt) production, is being explored for tx of CIT. Methods: This was the Ph I portion of a Ph I/II, blinded, pbo-controlled multicenter study in adults with solid tumors and baseline plts ≤300,000µL, who received up to 6 cycles of gem (1000-1250 mg/m² IV) as monotherapy on Days 1, 8, and 15 Q28 days or Days 1 and 8 Q21 days in combination with cisplatin (50-80 mg/m² IV Day 1 or divided 1 and 8) or carboplatin (AUC 4-7 IV Day 1). Patients received ctx alone for Cycle 1 and ctx plus epag or matching pbo (randomized 3:1) daily on Days -5 to -1 and 2 to 6 for subsequent cycles. Epag or pbo was interrupted for plts ≥400,000/µL. Results: 33 patients were randomized; 26 received epag or pbo (Table). Data review with an external, independent physician found no safety concerns, and there were sufficient plt increases with a dose of 100 mg epag vs pbo. No dose-limiting toxicities were reported for epag but 1 for pbo. Most AEs were grade 1 or 2. The most common AE in combined epag- and combined pbo-treated groups was neutropenia. Conclusions: Epag was well-tolerated and improved plt counts. Based on these encouraging Ph I results, Ph II using 100 mg epag in thrombocytopenic patients is planned.

	Gema		Gem + Cis/Carboa
	Pbo N=4	Epag N=10	Pbo N=3	Epag N=9
Any AEs, n (%)	3 (75)	10 (100)	3 (100)	9 (100)
Tx-related	1 (25)	5 (50)	2 (67)	3 (33)
≥ Grade 3	2 (50)	3 (30)	2 (67)	6 (67)
Liver AEs	0	1 (10)	0	2 (22)
Renal AEs	2 (50)	0	0	3 (33)
Thromboembolic eventsb	0	1 (10)	0	2 (22)
SAEs	1 (25)	2 (20)	1 (33)	5 (56)
Deaths, n (%)c	2 (50)	4 (40)<	1 (33)	3 (33)
Plts: Cycles 2-6, mean (n)
Pre ctx Day 1	309 (4)	443 (9)	314 (3)	442 (9)
Pre ctx Day 8	204 (4)	355 (10)	239 (2)	270 (9)
Pre ctx Day 15	75 (3)	164 (10)	-	-
Nadir	103 (4)	143 (10)	53 (2)	113 (9)
Grade 3/4 thrombocytopenia: Cycle 2-6, n (%)	1 (25)	0	2 (67)	3 (33)

^a 7/33 randomized pts never received epag/pbo. ^b None were considered related to epag and all resolved. One event occurred after stopping epag and following disease progression (PD). ^cAll deaths were from PD; three additional patients died prior to receiving epag or pbo.