Oncolytic vector

Therapeutic agent

Cancer type

Phase, study type

Mode of therapy

Purpose of the study

Status

Clinical trial number

DNX2401

DNX2401 in combination with temozolomide

Recurrent glioblastoma

Phase 1, open-label, single-group study

Intra-tumoral

Safety evaluation

Completed

NCT01956734

DNX2401 with interferon gamma

Recurrent glioblastoma

Phase 1b, open-label, parallel assignment

Intra-tumoral

Efficacy evaluation of DNX-2401

Completed

NCT02197169

DNX-2401

Diffuse pontine glioma

Phase 1, open-label, single-group study

Intra-tumoral

Safety evaluation and dose determination

Recruiting

NCT03178032

DNX-2401 in combination with pembrolizumab

Recurrent glioblastoma or gliosarcoma

Phase 2, multicenter, open-label study

Intra-tumoral DNX-2401 with intravenous pembrolizumab

Single dose efficacy evaluation of DNX-2401

Active, not recruiting

NCT02798406

ONCOS-102

ONCOS-102 in combination with cyclophosphamide

Advance cancers, malignant solid tumor

Phase 1, open-label, single-group study

Intra-tumoral ONCOS-102 with intravenous cyclophosphamide

Safety and dosage determination

completed

NCT01598129

ONCOS-102 in combination with pemetrexed/cisplatin or cyclophosphamide

Un-resectable malignant pleural mesothelioma

Randomized phase 1b or phase2 open-label, parallel group-study

Intra-tumoral ONCOS-102

Evaluation of safety, tolerability and efficacy of ONCOS-102 in combination with chemotherapy

Active, not recruiting

NCT02879669

ONCOS-102 in combination with pembrolizumab or cyclophosphamide

Advanced or un-resectable melanoma

Phase1, open-label, single-group study

Intra-tumoral ONCOS-102 with intra-venous pembrolizumab

Safety evaluation of sequential treatment with ONCOS-102 in combination with pembrolizumab

Recruiting

NCT03003676

VCN-01

VCN-01 in combination with gemcitabine and Abraxane

Patients with advanced solid tumors

Phase1, open-label, single-group study

Intra-venous administration of VCN-01 with gemcitabine

Safety and tolerability evaluation of VCN-01 in combination therapy

Active, not recruiting

NCT02045602

VCN-01

Refractory retinoblastoma

Phase 1, open-label, single-group study

Intra-vitreal injection of VCN-01

Safety and efficacy evaluation

Recruiting

NCT03284268

VCN-01 in combination with durvalumab

Recurrent head and neck squamous cell carcinoma

Phase 1, multicenter, open-label, dose-escalation study

Intra-venous injection of VCN-01 and durvalumab

Safety, tolerability and efficacy evaluation

Recruiting

NCT03799744

LOAd703

LOAd703 in combination with gemcitabine and nab-paclitaxel

Pancreatic cancer

Open-label, single-group phase 1/2 trial

Ultra-sound guided percutaneas injection of LOAd703

Safety evaluation

Recruiting

NCT02705196

LOAd703

Pancreatic, ovarian, biliary and colorectal cancer

Open-label, single-group, phase 1/2 study

Image-guided intra-tumoral injection of LoAd703

Evaluation of efficacy of LOAd703 in various cancers

Recruiting

NCT03225989

ColoAd1

ColoAd1

Resectable colon cancer, resectable non-small cell lung cancer, bladder cancer, renal cell carcinoma

Phase 1 study

Intra-tumoral injection or intravenous infusion of ColoAd1

Mechanism of action study

Completed

NCT02053220

ColoAd1

Solid tumor of epithelial origin, colorectal cancer, bladder cancer

Phase I, Phase II study

Sub-acute fractionated intravenous injection

Dose escalation study

Completed

NCT02028442

OBP-301

Telomelysin (OBP-301)

Esophago gastric adenocarcinoma

Phase 2 study

Intra-tumoral

Safety and efficacy study

Recruiting

NCT03921021

OBP-301 and pembrolizumab

Advanced solid tumor

Phase 1 study

Intra-tumoral

Safety and efficacy study

Recruiting

NCT03172819

OBP-301

Hepatocellular carcinoma

Phase 1 study

Intra-tumoral

Safety and efficacy study

Recruiting

NCT02293850

OBP-301

Melanoma Stage III/IV

Phase 2 study

Intra-lesion

Safety, efficacy evaluation

Active but not recruiting

NCT03190824

CG0070

CG0070

Bladder cancer (BOND2)

Phase 2 study

Intra-vesical therapy

Safety and efficacy study

Completed

NCT02365818

CG0070

Bladder cancer (ExBOND)

Phase 2 study

Intra-vesical therapy

Safety and efficacy study

Withdrawn

NCT02143804

CG0070

Carcinoma, transitional cell bladder neoplasms

Phase 1 study

Intra-vesical therapy

Evaluation of safety and dosing of CG0070

Current recruitment status is unknown

NCT00109655

Cancer type

Administration route

Groups

Patient Recovery

Adverse effects

CR

PR

SD

PD

NC

Hepatocellular carcinoma

Transartarial injection of Oncorine plus TACE

Oncorine + TACE

28.7%

32.2%

26.4%

12.6%

_

Not reported

TACE

14.8%

21.6%

38.6%

25%

_

Pancreatic cancer

Intratumoral (Oncorine),
gemitabine (intratumoral)

Oncorine + gemitabine

_

15.8%

52.6%

_

_

Fever and diarrhea

Non-small-cell lung cancer (NSCLC)

Intratumoral (Oncorine), vinorelbine/cispaltin
chemotherapy (NP)

Arm A (Oncorine+NP)

_

5 cases

10 cases

4 cases

_

Noninfectious fever, mild pneumothorax

Arm B (NP)

_

3 cases

9 cases

5 cases

_

Malignant pleural effusion

Intrathoracic injection of Oncorine/cisplatin

Oncorine group

10 cases

8 cases

_

3 cases

5 cases

Leukopenia

Cisplatin group (Control)

8 cases

6 cases

_

5 cases

7 cases

Oncolytic Vector

Therapeutic agent

Cancer type

Phase, study type

Mode of therapy

Purpose of the study

Status

Clinical trial number

T-VEC

T-VEC

Squamous cell carcinoma

Phase 2, single-group study

Injection of T-VEC into target lesions

efficacy evaluation

Recruiting

NCT03714828

T-VEC

Melanoma

Phase Ib, open-level, multicenter, single-arm study

Intra-tumoral injection of T-VEC in combination with
intravenous ipilimumab

To evaluate safety of T-VEC in combination with ipilimumab

Active, not recruiting

NCT01740297

Phase 2, open-label, multicenter, randomized study

Intra-tumoral injection of T-VEC in combination with
intravenous ipilimumab; intravenous ipilimumab alone

T-VEC + pembrolizumab

Head and neck squamous cell carcinoma

Phase 1b, open-label, multicenter, randomized study

Intralesional injection of T-VEC followed by intravenous
injection of pembrolizumab

Safety and efficacy evaluation in combination therapy

Active, not recruiting

NCT02626000

T-VEC

Unresected melanoma, stage IIIb, IV M1c

Phase 2, multicenter, single-arm study

Intralesional injection of T-VEC

Safety and tolerability evaluation

Active, not recruiting

NCT02366195

HF-10

HF-10 + ipilimumab

Unresectable or metastatic melanoma

Phase 2, single-group assignment study

Intra-tumoral injection of T-VEC, intravenous infusion of
ipilimumab

Efficacy and safety assessment

Completed

NCT02272855

HF-10 in combination with neoadjuvant nivolumab

Resectable stage IIIb, IIIC, IV M1a melanoma

Phase 2, open-label, single-group assignment

Intra-tumoral injection of HF-10, infusion of nivolumab
(subcutaneous or intravenous)

Evaluation of the safety and efficacy

Recruiting

NCT03259425

HF-10 in combination with gemcitabine and Nab-paclitaxel
or TS-1

Unresectable pancreatic cancer, stage III or IV

Phase 1, open label, multicenter study

Intra-tumoral injection of HF-10 and intravenous infusion
of gemcitabine and Nab-paclitaxel for stage III patients; intra-tumoral
injection of HF-10 in combination with oral TS-1 for stage IV patients

To determine the appropriate dose of HF-10 treatment in
combination with chemotherapy

Active but not recruiting

NCT03252808

HSV-1716

HSV-1716

Non-central nervous system solid tumor, relapsed sarcoma
and neuroblastoma

Phase 1, non-randomized, single-group assignment

Intra-tumoral

Dose-escalation study

Completed

NCT00931931

HSV-1716

Malignant pleural mesothelioma

Phase 1/IIa single-group open-label study

Intra-pleural delivery of HSV-1716

To study the safety and tolerability and biological
effects of the drug

Completed

NCT01721018

M03

M03

Recurrent malignant glioma

Phase I, single-group, open-label study

Intra-tumoral administration

To determine the safety and tolerability of the maximum
dose

Recruiting

NCT0206282

Oncolytic virus

Combination

Route of injection

References

Vaccinia virus

Pembrolizumab

Intratumoral

NCT04725331

Cyclophosphamide Avelumab

Intravenous

NCT02630368

Ipilimumab

Intratumoral

NCT02977156

Herpes simplex virus type 1

Pembrolizumab

Intratumoral

NCT03004183

Human adenovirus

HER2-specific CAR T cells

Intratumoral

NCT03740256

Valacyclovir Pembrolizumab radiation therapy

Intratumoral

NCT03004183

Reovirus

Monoclonal antibody targeting PD-1

Intravenous

NCT04445844

Atezolizumab

Intravenous

NCT04102618

Avelumab
Paclitaxel

Intravenous

NCT04215146

Class

Phase; Status

Delivery/ Location

Combinations

Age (Years)

Disease

Novel Aspects; Key findings

NCT

Herpes Simplex Virus

1; terminated

Peri- and intratumoral after tumor resection

IV dexamethasone prior to and 6 and 12 hrs post-surgery

 12–21

Refractory/recurrent HGG

Well tolerated but trial retracted after 2 pts enrolled

NCT02031965

1; completed

IT infusion over 6 hrs via 3–4 catheters

5 Gy radiation to tumor within 24 hrs after virus

 3–18

Progressive/recurrent supratentorial malignant glioma

First completed trial of OV for pediatric brain tumor; 12.2 month median overall survival. 5/12 patients lived ≥18 months post treatment. 10⁸ PFU safe and tolerable. Marked increase in TILs

NCT02457845

1; recruiting

IT via catheter

5 Gy radiation to tumor within 24 hrs of virus

 3–18

Refractory/recurrent malignant cerebellar tumors; includes LMD

 First OV delivered via catheter to the cerebellum; first trial of oHSV for infratentorial tumors

NCT03911388

2; not yet recruiting

IT infusion over 6 hrs via ≤4 catheters

5 Gy radiation to tumor

 3–21

Progressive/recurrent malignant HGG

 First phase 2 trial of OV in children

NCT04482933

Adenovirus

1; completed

IT infusion via catheter in cerebellar peduncle

Standard radiation and/or chemotherapy 3–4 wks after virus

1 −18

Naïve DIPG

Including OV as upfront therapy;
Safe and tolerable. All patients showed reduced tumor volume

NCT03178032

1b/2; recruiting

IV infusion; weekly × 8

Radiotherapy for naïve DIPG

1 – 21

Naïve DIPG; Relapsed/refractory MB

Cellular therapy

NCT04758533

Poliovirus

1b; active, not recruiting

IT infusion via intracerebral CED

12 – 21

Recurrent HGG/MB/ATRT

Disease involving cerebellum, pituitary, leptomeninges, brainstem, spinal cord, or requiring ventricular access can be included at discretion of neurosurgeon

NCT03043391

Reovirus

1; active, not recruiting

IV infusion over 60 min on days 3–5 of 28-day cycle × ≤ 12

SQ GM-CSF on days 1 and 2 of 28 day cycle. Total cycles ≤ 12

10–21

Refractory/relapsed HGG/MB/ATRT/PNET

IV virus delivery

NCT02444546

Measles Virus

1; recruiting

Locally for recurrent tumors;
Lumbar puncture for disseminated disease

1 – 39

Disseminated or locally recurrent MB; refractory ATRT

NIS allows noninvasive spatial and temporal virus tracking
Lumbar puncture delivery

NCT02962167

Study title

Trial number

Completion date

Reference

Efficacy and safety of Talimogene Laherparepvec neoadjuvant treatment plus surgery versus surgery alone for melanoma

NCT02211131

22 April

34

Biomarker analysis of neoadjuvant intralesional therapy in high-risk early melanoma Ph 2 Talimogene Laherparepvec

NCT04427306

24 May

38

Neoadjuvant combination immunotherapy for stage III melanoma

NCT03842943

22 March

40

A phase IIa study of neoadjuvant JX-594 (thymidine kinase-deactivated vaccinia virus plus GM-CSF) administered by intravenous infusion or intratumoral injection followed by surgical resection in patients with metastatic colorectal tumors within the liver

NCT01329809

13 March

43

Neoadjuvant intravesical NIS measles virus (MV-NIS) in patients undergoing cystectomy for urothelial carcinoma but ineligible for neoadjuvant cisplatin-based chemotherapy

NCT03171493

22 December

46

Safety and effectiveness study of G207, a tumor-killing virus, in patients with recurrent brain cancer

NCT00028158

3 October

A phase 1/2 study of Talimogene Laherparepvec in combination with neoadjuvant chemotherapy in triple-negative breast cancer NCT02779855 injected directly into the tumor during chemotherapy prior to surgery

NCT02779855

23 August

37

Stage IIIB/C/D–IV M1a melanoma with injectable disease

NCT04330430

23 August

39

Phase II neoadjuvant trial of nivolumab in combination with HF10 oncolytic viral therapy in resectable stage IIIB, IIIC, IVM1a melanoma (Neo-NivoHF10)

NCT03259425

20 September

41

Phase I study of intravesical recombinant fowlpox-GM-CSF (rF-GM-CSF) and/or recombinant fowlpox-TRICOM (rF-TRICOM) in patients with bladder carcinoma scheduled for cystectomy

NCT00072137

10 November

45

Vaccinia virus

Study design

Case number

Clinical outcome

Ref.

BN-CV301

Phase I; open-label, 3 + 3 design, dose-escalation trial.

12

Single-agent BN-CV301 produced a confirmed partial response (PR) in 1 patient and prolonged stable disease (SD) in multiple patients.

⁸²

rV-CEA(6D)-TRICOM/rF-CEA(6D)-TRICOM

Phase I; in Cycle 1, patients received thrice weekly s.c. injections of IFN-α-2b the week after rVCEA(6D)-TRICOM. In Cycles 2–4, patients received thrice weekly s.c. injections of IFN-α-2b the same week that rF-CEA(6D)-TRICOM was given.

33

No patients had a partial response, and eight patients exhibited SD of ≥3 months. Median progression-free survival and overall survival (OS) were 1.8 and 6.3 months, respectively. Significantly higher serum CD27 levels were observed after vaccine therapy and 42% of patients assayed developed CEA-specific T cell responses.

⁸³

Pexa-Vec (JX-594)

Phase Ib; single-center, open-label.

15

Pexa-Vec administered as biweekly intravenous infusion was safe and well-tolerated.

⁸⁴

vvDD

Phase I; open-label, dose-escalation trial using a single-dose group sequential dose-escalating design.

16

Intratumoral injection of the oncolytic vaccinia vvDD was well-tolerated in patients and resulted in selective infection of injected and noninjected tumors and antitumor activity.

⁸⁵

vvDD

Phase I; 11 patients were treated in three dose cohorts (3 × 108 pfu, 1 × 10⁹ pfu, or 3 × 109 pfu). vvDD was infused in 250 ml of bicarbonate-buffered saline over 1 hour.

Colon cancer 7; pancreatic cancer 2; hepatocellular carcinoma
1; melanoma 1;

No dose-limiting toxicities and treatment-related severe adverse events were observed. One patient
showed a mixed response on PET-CT with resolution of some liver metastases, and another patient with cutaneous melanoma demonstrated clinical regression of some lesions.

⁸⁶

MVA-5T4

Phase I/II; Patients randomized to a cyclophosphamide group received 50 mg twice daily
on treatment days 1 to 7 and 15 to 21. Patients randomized to a MVA-5T4 group received an intramuscular injection at a dose of 1 × 109 50% tissue culture infectious dose on treatment days 22, 36, 50, 64, 78, and 106.

55

Cyclophosphamide depleted regulatory T cells in 24 of 27 patients receiving MVA-5T4, prolonging PFS (5.0 vs 2.5 months; hazard ratio [HR], 0.48; 95% CI, 0.21–1.11; P = .09). MVA-5T4 doubled baseline anti-5T4 responses in 16 of 35 patients, resulting in prolonged PFS (5.6 vs 2.4 months; HR, 0.21; 95% CI, 0.09–0.47; P < .001) and OS.

⁸⁷

TroVax

Phase I/II; an open-label upward titration study of TroVax given to patients via i.m. injection. In addition, a single dose level of TroVax, administered i.d., was included to explore the potential effect of this route on safety and immunogenicity.

22

TroVax was able to boost 5T4-specific immune responses in the presence of MVA-neutralizing antibodies. A positive association between the development of a 5T4 (but not MVA) antibody response and patient survival or time to disease progression.

⁸⁸

TroVax

Phase II; an open label study of TroVax administered by i.m. injection to patients with advanced colorectal cancer receiving 5-FU/folinic acid plus oxaliplatin as first-line therapy.

17

Administration of TroVax alongside 5-fluorouracil, folinic acid, and oxaliplatin was safe and well tolerated with no serious adverse events. Of the 11 evaluable patients, 6 had complete or partial responses. 5T4-specific immune responses, but not MVA-specific immune responses, correlated with clinical benefit.

⁸⁹

TroVax

Phase II; an open label study of TroVax administered by intramuscular injection to patients with advanced colorectal cancer receiving 5-FU, leukovorin and irinotecan as Wrst line therapy.

19

Administration of TroVax alongside chemotherapy was safe and well tolerated with no SAEs.