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ADENOVIRUS 5 AS A DELIVERY VECTOR
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Table 1. Trial characteristics and associated adverse events
Trials (n = 39)
Patients (n = 756)
Co-treatmentb
Ad5 alone
Surgery
Radiation
Chemotherapy
Dosesc
Single
Multiple
Mechanism of action
Suicide
Oncolytic
Immunomodulatory
Tumor suppressor
Oncolytic/suicide
Clinical trial subsets
Unedited AE
Drug-related AE
Most frequent AE
Phase
I
I/II
II
Cancer type
Prostate
Glioma/GBM
HNSCC
Pancreasb
NSCLC
Breastd
Melanomad
Sarcoma
Cutaneous B cell lymphoma
Hepatobiliary
Liver metastasis
Solid
14 (35.9%)
23 (59.0%)
11 (28.2%)
10 (25.6%)
7 (17.9%)
6 (15.4%)
5 (12.8%)
21 (53.8%)
11 (28.2%)
9 (23.1%)
25 (64.1%)
5 (12.8%)
9 (23.1%)
9 (23.1%)
6 (15.4%)
6 (15.4%)
4 (10.3%)
4 (10.3%)
2 (5.1%)
2 (5.1%)
2 (5.1%)
1 (2.6%)
1 (2.6%)
1 (2.6%)
1 (2.6%)
241 (31.9%)
469 (62.0%)
174 (23.0%)
243 (32.1%)
171 (22.6%)
108 (14.3%)
60 (7.9%)
409 (54.1%)
166 (22.0%)
181 (23.9%)
426 (56.3%)
145 (1.92%)
185 (24.5%)
138 (18.3%)
127 (16.8%)
137 (18.1%)
130 (17.2%)
83 (11.0%)
24 (3.2%)
37 (4.9%)
20 (2.6%)
13 (1.7%)
19 (2.5%)
16 (2.1%)
12 (1.6%)
205 (26.8%)
540 (70.5%)
115 (15%)
240 (31.3%)
237 (30.9%)
138 (18%)
37 (4.9%)
509 (66.4%)
83 (10.9%)
175 (22.9%)
409 (53.4%)
169 (22.1%)
189 (24.7%)
59 (7.7%)
78 (10.2%)
219 (28.6%)
176 (23%)
109 (14.3%)
60 (7.9%)
2 (0.3%)
26 (3.4%)
1 (0.2%)
5 (0.7%)
2 (0.3%)
9 (1.2%)
97 (20.8%)
367 (78.5%)
92 (19.7%)
168 (35.9%)
61 (13.1%)
113 (24.2%)
34 (7.3%)
317 (67.8%)
67 (14.4%)
84 (18%)
289 (61.8%)
17 (3.7%)
162 (34.7%)
56 (12%)
17 (3.7%)
187 (40%)
73 (15.6%)
92 (19.7%)
3 (0.7%)
2 (0.5%)
15 (3.3%)
1 (0.3%)
4 (0.9%)
2 (0.5%)
91 (19.5%)
aOnly trials that reported separate AE.
bTrials with multiple co-treatments are counted individually.
cTrials with multiple and single dosed arms are excluded.
dOne clinical trial reported breast and melanoma AE combined, reported, in this study, under breast.
Ad5, Adenovirus 5; AE, adverse events; HNSCC, head and neck squamous cell cancer; NSCLC, non-small cell lung cancer.
As reported in Table 1, these trials encompass a variety of
cancers: most commonly, prostate (9 trials), glioma or
glioblastoma (6 trials), head and neck squamous cell
cancer (HNSCC, 6 trials), and pancreas (4 trials). The
majority of trials was phase I (25 trials) with 9 phase II
trials. The Ad5 drug was given at varying dose levels,
either in viral particles (vp, range 10e7-10e13) per injection
or plaque-forming unit (pfu, range 10e6-10e12),
but AE were not reported by dose level.
The trials included several mechanisms of action for the
experimental Ad5-packaged drug with 17 (43.6%) trials
using replication-competent adenovirus. There were 13
trials that investigated treatment with the experimental
Ad5-packaged drug alone versus 12 trials that co-treated
with chemotherapy, 16 with radiation, and 11 with surgery.
If a clinical trial co-treated with multiple modalities,
the sequence was chemotherapy followed by radiation and
surgery. There were two trials that used different cotreatment
modalities consisting of surgery versus chemoradiation,
which were counted individually in the
analysis.
CTCAE categories were used to report AE, but each
trial varied in the number of categories that were reported
(average 20.8, range 5-69). To limit site specific AE (i.e.,
mucositis) and ensure that the most frequent AE did occur
over a broad range of trials, the most frequent AE were
analyzed only if the category was reported in 10 or more
trials.
Primary Outcome
Out of all 756 patients (Table 1), there were 3 (0.4%)
grade 5 (mortalities) reported. All three deaths were in
patients co-treated with both chemotherapy and radiation.
In addition, all three patients received multiple doses of an
immunomodulatory packaged Ad5 drug. Two deaths, one
due to splenic artery thrombosis and one to progression of
8 (9.4%)
77 (89.6%)
14 (16.3%)
34 (39.6%)
10 (11.7%)
25 (29.1%)
3 (3.5%)
62 (72.1%)
16 (18.7%)
8 (9.4%)
50 (58.2%)
9 (10.5%)
27 (31.4%)
3 (3.5%)
1 (1.2%)
31 (36.1%)
17 (19.8%)
17 (19.8%)
11 (12.8%)
1 (1.2%)
1 (33.4%)
2 (66.7%)
3 (100%)
13 (35.9%)
11 (28.2%)
16 (41.0%)
12 (30.8%)
267 (35.3%)
187 (24.7%)
268 (35.8%)
220 (29.1%)
Grade ‡3(n = 767)
167 (21.8%)
177 (23.1%)
285 (37.2%)
409 (53.4%)
Grade 3a (n = 468)
91 (19.5%)
95 (20.3%)
187 (40%)
265 (56.7%)
Grade 4a (n = 86)
14 (16.3%)
22 (25.6%)
32 (37.3%)
57 (66.3%)
Grade 5a (n = 3)
3 (100%)
3 (100%)
3 (100%)
3 (100%)
1 (33.4%)
2 (66.7%)
Human Gene Therapy - April 2023

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