A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE)

Machiels, Jean-Pascal; Salazar, Ramon; Rottey, Sylvie; Duran, Ignacio; Dirix, Luc; Geboes, Karen; Wilkinson-Blanc, Christine; Pover, Gillian; Alvis, Simon; Champion, Brian; Fisher, Kerry; McElwaine-Johnn, Hilary; Beadle, John; Calvo, Emiliano

doi:10.1186/s40425-019-0510-7

Table 1 TEAE^a summary following enadenotucirev infusion

From: A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE)

Category	Preferred term	Number (%) of patients reporting AEs				Number of TEAEs grade ≥ 3 (all dosing groups)
		Dose assigned (vp)
		< 1 × 10¹² vp (n = 6)	1–3 × 10¹² vp (n = 26)	> 3 × 10¹² vp (n = 29)	All dosing groups (N = 61)
Any TEAE		6 (100) [4]	26 (100) [25]	29 (100) [29]	61 (100) [58]	161 [90]
Any SAE		1 (16.7)	7 (26.9) [4]	12 (41.4) [6]	20 (32.8) [10]
TEAEs of interest^b
Influenza-like symptoms	Chills, n (%)	0	18 (69.2) [18]	23 (79.3) [23]	41 (67.2) [41]	0
	Influenza-like illness, n (%)	0	7 (26.9) [7]	6 (20.7) [6]	13 (21.3) [13]	0
	Pyrexia, n (%)	2 (33.3) [1]	20 (76.9) [19]	23 (79.3) [23]	45 (73.8) [43]	2 [2]
Acute respiratory symptoms	Acute lung injury, n (%)	0	0	1 (3.4) [1]	1 (1.6) [1]	1 [1]
	Dyspnea, n (%)	1 (16.7)	6 (23.1) [2]	7 (24.1) [3]	14 (23.0) [5]	3 [2]
	Hypoxia, n (%)	0	1 (3.8) [1]	5 (17.2) [5]	6 (9.8) [6]	9 [9]
	Interstitial lung disease, n (%)	0	0	1 (3.4) [1]	1 (1.6) [1]	1 [1]
Renal events	Acute kidney injury, n (%)	0	1 (3.8)	3 (10.3) [2]	4 (6.6) [2]	1
	Blood creatinine increased, n (%)	0	0	2 (6.9) [1]	2 (3.3) [1]	0
	Glomerulonephritis membranoproliferative, n (%)	0	0	1 (3.4) [1]	1 (1.6) [1]	0
	Nephrotic syndrome, n (%)	0	1 (3.8) [1]	0	1 (1.6) [1]	1 [1]
	Proteinuria, n (%)	0	5 (19.2) [4]	5 (17.2) [5]	10 (16.4) [9]	1 [1]
	Renal failure, n (%)	0	0	1 (3.4) [1]	1 (1.6) [1]	0
Hepatic events	ALT increased, n (%)	1 (16.7)	1 (3.8) [1]	12 (41.4) [11]	14 (23.0) [12]	4 [4]
	AST increased, n (%)	2 (33.3)	2 (7.7) [1]	10 (34.5) [9]	14 (23.0) [10]	5 [4]
	Transaminases increased, n (%)	0	2 (7.7) [2]	2 (6.9) [2]	4 (6.6) [4]	1 [1]
Coagulation disorders	aPTT, n (%)	0	2 (7.7) [2]	5 (17.2) [4]	7 (11.5) [6]	1 [1]
	Fibrin D-dimer increased, n (%)	0	5 (19.2) [4]	9 (31.0) [8]	14 (23.0) [12]	5 [4]
	International normalized ratio increased, n (%)	1 (16.7)	1 (3.8) [1]	3 (10.3) [2]	5 (8.2) [3]	0
Hematological events	Anemia, n (%)	1 (16.7)	6 (23.1) [2]	9 (31.0) [2]	16 (26.2) [4]	5 [1]
	Leukopenia/WBC count decreased, n (%)	0	3 (11.5) [3]	0	3 (4.9) [3]	0
	Lymphopenia/lymphocyte count decreased, n (%)	0	4 (15.4) [4]	2 (6.9) [2]	6 (9.8) [6]	8 [7]
	Neutropenia/neutrophil count decreased, n (%)	0	2 (7.7) [2]	5 (17.2) [5]	7 (11.5) [7]	7 [7]
	Thrombocytopenia/ platelet count decreased, n (%)	1 (16.7) [1]	5 (19.2) [5]	13 (44.8) [13]	19 (31.1) [19]	4 [4]
	Any TEAE relating to WBC count, n (%)	0	6 (23.1) [6]	6 (20.7) [6]	12 (19.7) [12]	0

ALT alanine aminotransferase; aPTT activated partial thromboplastin time; AST aspartate aminotransferase; N (n) number of patients, SAE serious adverse event, TEAE treatment-emergent adverse event; vp viral particle(s); WBC white blood cell
^aTEAEs are defined as any adverse event that occurs after the first administration of study treatment and through the end of the reporting period, any event that is considered treatment-related regardless of the start date of the event, or any event that is present at baseline and continues after the first dose of study treatment but worsens in intensity
^bSelected preferred terms categorized as acute respiratory, renal, related to laboratory tests of hepatic transaminases, coagulation and hematological parameters, which were commonly related to study treatment
Numbers in bold and square brackets [] are the number of patients or number of events that were possibly, probably, or definitely related to study treatment

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