Table 2 (A): Dose-limiting toxicities. (B): Adverse events, suspected to be study drug related by preferred term. (C): Grade ≥ 3 serious adverse events, regardless of study drug relationship by preferred term.

Table 2(B)	Adverse events, suspected to be study drug related by preferred term^a
Preferred term, n (%)	All LXS196 QD patients n = 38		All LXS196 BID patients n = 30		LXS196 300 mg BID (RDE) patients n = 18		All LXS196 patients N = 68
Preferred term, n (%)	All grades	Grade ≥ 3	All grades	Grade ≥ 3	All grades	Grade ≥ 3	All grades	Grade ≥ 3
Number of patients with ≥ 1 adverse event	35 (92.1)	11 (28.9)	28 (93.3)	6 (20.0)	17 (94.4)	2 (11.1)	63 (92.6)	17 (25.0)
Nausea	26 (68.4)	1 (2.6)	19 (63.3)	0	14 (77.8)	0	45 (66.2)	1 (1.5)
Diarrhoea	15 (39.5)	0	16 (53.3)	1 (3.3)	11 (61.1)	1 (5.6)	31 (45.6)	1 (1.5)
Vomiting	12 (31.6)	1 (2.6)	9 (30.0)	0	7 (38.9)	0	21 (30.9)	1 (1.5)
Alanine aminotransferase increased	7 (18.4)	2 (5.3)	8 (26.7)	2 (6.7)	5 (27.8)	1 (5.6)	15 (22.1)	4 (5.9)
Hypotension	8 (21.1)	5 (13.2)	7 (23.3)	1 (3.3)	3 (16.7)	0	15 (22.1)	6 (8.8)
Fatigue	10 (26.3)	0	4 (13.3)	0	3 (16.7)	0	14 (20.6)	0
Asthenia	6 (15.8)	0	7 (23.3)	0	4 (22.2)	0	13 (19.1)	0
Aspartate aminotransferase increased	5 (13.2)	2 (5.3)	6 (20.0)	2 (6.7)	3 (16.7)	1 (5.6)	11 (16.2)	4 (5.9)
Dry skin	2 (5.3)	0	6 (20.0)	0	4 (22.2)	0	8 (11.8)	0
Rash	3 (7.9)	0	5 (16.7)	0	4 (22.2)	0	8 (11.8)	0
Blood creatinine increased	2 (5.3)	0	5 (16.7)	0	2 (11.1)	0	7 (10.3)	0
Constipation	4 (10.5)	0	3 (10.0)	0	1 (5.6)	0	7 (10.3)	0

Table 2(C)	Grade ≥ 3 serious adverse events, regardless of study drug relationship by preferred term
Preferred term, n (%)	LXS196 100 mg QD	LXS196 200 mg QD	LXS196 300 mg QD	LXS196 500 mg QD	LXS196 800 mg QD	LXS196 1000 mg QD	All LXS196 QD patients	LXS196 200 mg BID patients	LXS196 300 mg BID (RDE) patients	LXS196 400 mg BID patients	All LXS196 BID patients	All LXS196 patients
Preferred term, n (%)	n = 3	n = 4	n = 15	n = 11	n = 1	n = 4	n = 38	n = 6	n = 18	n = 6	n = 30	N = 68
Number of patients with ≥ 1 adverse event	0	1 (25.0)	0	3 (27.3)	1 (100)	2 (50.0)	7 (18.4)	1 (16.7)	5 (27.8)	1 (16.7)	7 (23.3)	14 (20.6)
Hypotension	0	0	0	3 (27.3)	1 (100)	1 (25.0)	5 (13.2)	0	0	1 (16.7)	1 (3.3)	6 (8.8)
Pneumonia	0	1 (25.0)	0	0	0	1 (25.0)	2 (5.3)	0	1 (5.6)	0	1 (3.3)	3 (4.4)
Acute kidney injury	0	0	0	0	0	0	0	0	1 (5.6)	0	1 (3.3)	1 (1.5)
Cellulitis	0	0	0	0	0	0	0	1 (16.7)	0	0	1 (3.3)	1 (1.5)
Constipation	0	0*	0	0	0	0	0^b	0	0	0	0	0^b
Diarrhoea	0	0	0	0^b	0	0	0^b	0	0	0	0	0^b
Eyelid bleeding	0	0	0	0	0	0	0	0	1 (5.6)	0	1 (3.3)	1 (1.5)
Hepatic failure	0	0	0	0	0	0	0	0	1 (5.6)	0	1 (3.3)	1 (1.5)
Hepatic cytolysis	0	0	0	0	0	0	0	0	1 (5.6)	0	1 (3.3)	1 (1.5)
Nausea	0	1 (25.0)	0	0	0	0	1 (2.6)	0	0	0	0	1 (1.5)
Neutrophil count decreased	0	0	0	0	0	0	0	0	1 (5.6)	0	1 (3.3)	1 (1.5)
Oedema peripheral	0	0	0	0	0	0	0	0	1 (5.6)	0	1 (3.3)	1 (1.5)
Rash pruritic	0	0	0	0	0	0	0	0	1 (5.6)	0	1 (3.3)	1 (1.5)
Thrombocytopenia	0	0	0	0	0	0	0	0	1 (5.6)	0	1 (3.3)	1 (1.5)
Vomiting	0	1 (25.0)	0	0	0	0	1 (2.6)	0	0	0	0	1 (1.5)

Table 2(A): BID twice a day, DLT dose-limiting toxicity, QD, once daily.
Table 2(B): A patient with multiple severity grades for an adverse event is only counted under the maximum grade. MedDRA version 24.1, CTCAE version 4.03.
BID twice a day, CTCAE common terminology criteria for adverse events, MedDRA medical dictionary for regulatory activities, QD once daily, RDE recommended dose for expansion.
^aAll grade adverse events occurring in ≥10% “All LXS196 patients”.
Table 2(C): All serious adverse events were CTCAE grade ≥3 with an exception noted below.
^bTwo patients experienced CTCAE grade 1/2 events of constipation/diarrhoea, which were reported as serious adverse events.
A patient with multiple occurrences of an AE under one treatment is counted only once in the adverse event category for that treatment.
A patient with multiple adverse events is counted only once in the total row.
BID twice a day, CTCAE common terminology criteria for adverse events, QD once daily, RDE recommended dose for expansion.

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