Phase 1/2 study of epacadostat in combination with ipilimumab in patients with unresectable or metastatic melanoma

Gibney, Geoffrey T.; Hamid, Omid; Lutzky, Jose; Olszanski, Anthony J.; Mitchell, Tara C.; Gajewski, Thomas F.; Chmielowski, Bartosz; Hanks, Brent A.; Zhao, Yufan; Newton, Robert C.; Maleski, Janet; Leopold, Lance; Weber, Jeffrey S.

doi:10.1186/s40425-019-0562-8

Table 3 Safety Summary

From: Phase 1/2 study of epacadostat in combination with ipilimumab in patients with unresectable or metastatic melanoma

Patient, n (%)	25 mg BID (n = 8)	50 mg BID Cont’ (n = 18)	50 mg BID Int’ (n = 9)	75 mg Total Daily (n = 7)	100 mg BID^a (n = 1)	300 mg BID^a (n = 7)	Total (N = 50)
A. Treatment-Emergent Adverse Events
Any grade (≥10% of total patients)
Fatigue	6 (75.0)	13 (72.2)	5 (55.6)	4 (57.1)	0	4 (57.1)	32 (64.0)
Rash^b	4 (50.0)	10 (55.6)	1 (11.1)	6 (85.7)	0	5 (71.4)	26 (52.0)
Constipation	1 (12.5)	8 (44.4)	2 (22.2)	3 (42.9)	0	6 (85.7)	20 (40.0)
Pruritus^c	1 (12.5)	6 (33.3)	5 (55.6)	3 (42.9)	0	4 (57.1)	19 (38.0)
Diarrhea	3 (37.5)	6 (33.3)	3 (33.3)	3 (42.9)	0	2 (28.6)	17 (34.0)
Nausea	4 (50.0)	4 (22.2)	4 (44.4)	1 (14.3)	0	3 (42.9)	16 (32.0)
ALT elevation	2 (25.0)	3 (16.7)	2 (22.2)	2 (28.6)	0	5 (71.4)	14 (28.0)
Decreased appetite	0	5 (27.8)	4 (44.4)	2 (28.6)	0	2 (28.6)	13 (26.0)
Headache	5 (62.5)	6 (33.3)	0	1 (14.3)	0	1 (14.3)	13 (26.0)
AST elevation	2 (25.0)	3 (16.7)	1 (11.1)	1 (14.3)	0	5 (71.4)	12 (24.0)
Vomiting	1 (12.5)	5 (27.8)	3 (33.3)	2 (28.6)	0	1 (14.3)	12 (24.0)
Cough	4 (50.0)	3 (16.7)	2 (22.2)	0	0	2 (28.6)	11 (22.0)
Arthralgia	3 (37.5)	1 (5.6)	3 (33.3)	1 (14.3)	0	2 (28.6)	10 (20.0)
Pyrexia	2 (25.0)	3 (16.7)	2 (22.2)	1 (14.3)	0	1 (14.3)	9 (18.0)
Abdominal pain	2 (25.0)	3 (16.7)	1 (11.1)	1 (14.3)	0	1 (14.3)	8 (16.0)
Insomnia	1 (12.5)	4 (22.2)	0	2 (28.6)	0	1 (14.3)	8 (16.0)
Chills	3 (37.5)	1 (5.6)	1 (11.1)	1 (14.3)	0	1 (14.3)	7 (14.0)
Dizziness	1 (12.5)	3 (16.7)	1 (11.1)	1 (14.3)	0	1 (14.3)	7 (14.0)
Anemia	1 (12.5)	1 (5.6)	1 (11.1)	1 (14.3)	0	2 (28.6)	6 (12.0)
Myalgia	2 (25.0)	2 (11.1)	0	0	0	2 (28.6)	6 (12.0)
Hypothyroidism	2 (25.0)	3 (16.7)	0	0	0	0	5 (10.0)
Upper respiratory tract infection	0	2 (11.1)	0	3 (42.9)	0	0	5 (10.0)
Grade 3/4 (> 1 patient total)
ALT elevation	0	2 (11.1)	0	1 (14.3)	0	5 (71.4)	8 (16.0)
AST elevation	1 (12.5)	2 (11.1)	0	1 (14.3)	0	4 (57.1)	8 (16.0)
Colitis	2 (25.0)	1 (5.6)	1 (11.1)	0	0	0	4 (8.0)
Fatigue	0	2 (11.1)	1 (11.1)	0	0	0	3 (6.0)
Anemia	0	0	1 (11.1)	0	0	1 (14.3)	2 (4.0)
Confusional state	0	2 (11.1)	0	0	0	0	2 (4.0)
Hyperglycemia	0	1 (5.6)	0	1 (14.3)	0	0	2 (4.0)
Hypernatremia	0	1 (5.6)	0	1 (14.3)	0	0	2 (4.0)
Hypotension	0	2 (11.1)	0	0	0	0	2 (4.0)
Pruritus^c	0	1 (5.6)	0	0	0	1 (14.3)	2 (4.0)
Urinary tract infection	1 (12.5)	0	1 (11.1)	0	0	0	2 (4.0)
B. Immune-Related Adverse Events
Any grade (≥10% of total patients)
Rash^b	4 (50.0)	10 (55.6)	1 (11.1)	5 (71.4)	0	5 (71.4)	25 (50.0)
ALT elevation	2 (25.0)	3 (16.7)	2 (22.2)	2 (28.6)	0	5 (71.4)	14 (28.0)
Pruritus^c	1 (12.5)	5 (27.8)	3 (33.3)	1 (14.3)	0	4 (57.1)	14 (28.0)
AST elevation	2 (25.0)	3 (16.7)	1 (11.1)	1 (14.3)	0	5 (71.4)	12 (24.0)
Hypothyroidism	2 (25.0)	3 (16.7)	0	0	0	0	5 (10.0)
Grade 3/4 (> 1 patient total)
ALT elevation	0	2 (11.1)	0	1 (14.3)	0	5 (71.4)	8 (16.0)
AST elevation	1 (12.5)	2 (11.1)	0	1 (14.3)	0	4 (57.1)	8 (16.0)
Colitis	2 (25.0)	1 (5.6)	1 (11.1)	0	0	0	4 (8.0)
Pruritus^c	0	1 (5.6)	0	0	0	1 (14.3)	2 (4.0)

ALT alanine aminotransferase, AST aspartate aminotransferase, BID twice daily, cont’ continuous, int’ intermittent, MedDRA Medical Dictionary for Regulatory Activities
^a Epacadostat 100-mg BID and 300-mg BID dose cohorts were not re-explored in this study after protocol amendment to evaluate lower doses of epacadostat
^b Rash included the following MedDRA preferred terms: rash, rash maculopapular, rash pruritic, rash generalized, and rash macular; patients were counted only once (a patient with multiple terms for rash was counted only once for the term “rash”)
^c Pruritus included the following MedDRA preferred terms: pruritus and pruritus generalized; patients were counted only once (a patient with multiple terms for pruritus was counted only once for the term “pruritus”)

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