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. 2019 Jul 18;33(5):485–501. doi: 10.1007/s40259-019-00367-0

Table 2.

Timing of oncolytic virotherapy and immune checkpoint inhibitor combinations in selected clinical trials

Virus family Virus Indication Combination drug Virus RoA Dosing schedule Timing comment ClinicalTrials.gov identifier
Adenovirus Ad-p53 HNSCC Nivolumab IT

3 × virus (week 1), nivolumab day 5

Combination repeats on week 1 of each cycle q4w

Delayed ICI (4 days) NCT03544723
DNX-2401 GBM, gliosarcoma Pembrolizumab IT

Virus day 1

Pembrolizumab day ~ 8, q3w

Delayed ICI (1 week) NCT02798406
Enadenotucirev Advanced epithelial tumors Nivolumab IV

Unknown virus schedule

Unknown nivolumab schedule

Unknown NCT02636036
ONCOS-102 Anti-PD1-refractory metastatic melanoma

Cyclophosphamide

Pembrolizumab

IT

Cyclophosphamide day – 1

Virus days 1, 4, 8

Pembrolizumab day 22, q3w

Delayed ICI (3 weeks) NCT03003676
VCN-01 R/M HNSCC Durvalumab IV

Arm 1: virus IV day 1, durvalumab IV day 1, q4w

Arm 2: virus IV day 1, durvalumab IV day 15, q4w

Simultaneous ICI or delayed ICI (2 weeks) NCT03799744
CVA21 Cavatak Uveal melanoma with liver metastases Ipilimumab IV

Virus days 1, 3, 8, q3w (up to 19 ×)

Ipilimumab day 8, q3w (up to 4 ×)

Delayed ICI (1 week) NCT03408587
Cavatak Advanced melanoma Pembrolizumab IT

Virus days 1, 3, 8, q3w (up to 19 ×)

Pembrolizumab day 8, q3w (up to 2 years)

Delayed ICI (1 week) NCT02565992
Cavatak NSCLC Pembrolizumab IV

Virus days 1, 3, 8, q3w (up to 8 ×)

Pembrolizumab q3w (up to 24 months)

Uncertain NCT02824965
HSV1 HF-10 Resectable advanced melanoma Nivolumab IT neoadjuvant

9 × virus (5 × virus q1w then 4 × virus q2w)

Nivolumab q2w × 7, surgery, nivolumab q4w up to 1 year

Uncertain NCT03259425
T-VEC Early breast cancer Atezolizumab Unknown

Virus days 1, 21, q2w

Atezolizumab day 21, q2w

Delayed ICI NCT03802604
T-VEC TNBC, CRC with liver metastases Atezolizumab IT

Virus day 1, q3w

Atezolizumab day 1, q3w

Simultaneous ICI NCT03256344
T-VEC

Refractory lymphoma

Advanced or refractory non-melanoma skin cancer

Nivolumab IT

Virus days 1, 21, q2w

Nivolumab day 21, q2w

Delayed ICI (3 weeks) NCT02978625
T-VEC Malignant pleural effusion Nivolumab Intrapleural Virus (unknown schedule) ± nivolumab (same day as virus) Simultaneous ICI NCT03597009
T-VEC Advanced melanoma Pembrolizumab IT

Virus day 1, q3w

Pembrolizumab day 1, q3w

Simultaneous ICI NCT02965716
T-VEC Unresected melanoma Pembrolizumab IT

Virus days 1, 21, q2w

Pembrolizumab week 5, q3w

Delayed ICI (5 weeks) NCT02263508
RP1 Melanoma, bladder, skin, MSI-high solid Nivolumab IT

3 × virus in escalating doses q2w

Unknown nivolumab schedule

Unknown NCT03767348
Maraba MG1-E6/E7 HPV-associated cancer

Ad-E6/E7

Atezolizumab

IV or IT + IV

Prime IM Ad-E6/E7 (– 14 days)

4 × IV MG1-E6/E7 (spread over 2 weeks) OR IV MG1-E6/E7 day 1, IT MG1-E6/E7 days 4,14

Atezolizumab day 43, q3w

Delayed ICI (6 weeks) NCT03618953
MG1-MAGEA3 Metastatic melanoma, CSCC

Ad-MAGEA3

Pembrolizumab

Cyclophosphamide

IV or IT + IV

Ad-MAGEA3 IM day 1 ± CPA day – 3

Virus IV days 15,18, or IV day 15, IT days 22, 29, 36 (+ day 43, q3w IT boosters)

Pembrolizumab q3w (start either day 1 or week 6)

Pre-virus ICI (– 2 weeks) or delayed ICI (4 weeks) NCT03773744
Reovirus Reolysin Advanced pancreatic adenocarcinoma

Chemotherapy

Pembrolizumab

IV

Virus days 1, 2 q3w

Chemotherapy combination day 1 q3w

Pembrolizumab day 8 q3w

Delayed ICI (1 week) NCT02620423
Reolysin Advanced pancreatic cancer Pembrolizumab IV

Virus days 1, 2, 3, 8 + days 1, 8 q3w (up to 24 months)

Pembrolizumab day 1, q3w

Simultaneous ICI NCT03723915
Vaccinia PexaVec Unresectable RCC Cemiplimab IV or IT

3 × virus IT q2w or 4 × virus IV q1w, cemiplimab q3w

Cemiplimab q3w: @PD, 3 × virus IT q2w

Uncertain NCT03294083
PexaVec Refractory CRC

Durvaumab

Tremelimumab

IV

Virus days 2, 12, 16 cycle 1, day 2 cycle 2

Durvalumab day 1 each cycle

Tremelimumab day 1 cycles 1–4

Simultaneous ICI NCT03206073
PexaVec Advanced solid tumors Ipilimumab IT

Virus up to 5 × (weeks 1, 3, 5, 9, + week 12 if PD)

Ipilimumab up to 4 × IT (weeks 3, 5, 9, + week 12 if PD)

Delayed ICI (3 weeks) NCT02977156
PexaVec HCC Nivolumab IT

Virus days 1, 15, 29

Nivolumab day 15 q2w

Delayed ICI (2 weeks) NCT03071094
VSV VSV-IFNβ-NIS Solid Tumors Avelumab IV Virus day 1, avelumab day 1, q3w Simultaneous ICI NCT02923466
VSV-IFNβ-NIS HNSCC, NSCLC Pembrolizumab IV Virus day 1, pembrolizumab day 1, q3w Simultaneous ICI NCT03647163

CPA cyclophosphamide, CRC colorectal cancer, CSCC cutaneous squamous cell carcinoma, CVA21 coxsackievirus A21, GBM glioblastoma, HCC hepatocellular carcinoma, HNSCC head and neck squamous cell carcinoma, HPV human papillomavirus, HSV1 herpes simplex virus 1, ICI immune checkpoint inhibitor, IM intramuscular, IT intratumoral, IV intravenous, MAGEA3 melanoma-associated antigen 3, MSI microsatellite instability, NSCLC non-small cell lung carcinoma, PD progressive disease, PD1 programmed death 1, qxw every x weeks, RCC renal cell carcinoma, R/M recurrent/metastatic, RoA route of administration, TNBC triple-negative breast cancer, T-VEC talimogene laherparepvec, VSV-IFNβ-NIS vesicular stomatitis virus expressing both interferon β and sodium iodide symporter genes