Neoplasms

All Conditions

Nervous System Diseases

Infections

Rare Diseases

Glioblastoma

Glioma

Brain Neoplasms

Astrocytoma

Adenoviridae Infections

Oligodendroglioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Oligoastrocytoma

Anaplastic Oligoastrocytoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

BIRC5 protein, human

Patients with unresectable tumors will undergo a biopsy followed by injection of neural stem cells loaded with the virus and then receive standard chemoradiotherapy.

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus and then receive standard chemoradiotherapy.

The primary objectives are to evaluate the safety of the combined therapy and determine the maximum tolerated dose (MTD) for a future Phase II study.

Neural stem cells loaded with an oncolytic adenovirus

Maciej S Lesniak, MD

Malignant gliomas have a very poor prognosis with median survival measured in months rather than years. It is a disease in great need of novel therapeutic approaches. Based on the encouraging results of our preclinical studies which demonstrate improved efficacy without added toxicity, the paradigm of delivering a novel oncolytic adenovirus via a neural stem cell line in combination with radiation and chemotherapy is well-suited for evaluation in newly diagnosed malignant gliomas. The standard-of-care allows application of virotherapy as neoadjuvant therapy and assessment of the cooperative effects with radiation/chemotherapy without altering the standard treatment.

This is an open-label, phase 1, dose escalation trial that followed a 3x3 design. Three doses will be evaluated in the resectable cohorts: Cohort 1: 0.5x10\^8 NSCs loading 6.25x10\^10 vp; Cohort 2: 1.0x10\^8 NSCs loading 1.25x10\^11 vp; and Cohort 3: 1.5x10\^8 NSCs loading 1.875x10\^11 vp. Subjects enrolled have newly diagnosed high-grade glioma based on clinical and radiologic criteria; pathology will be confirmed at the time of surgical resection. Direct intra-tumoral injection of study product (NSC-CRAd-S-p7) will be done after resection but prior to closure. Subjects will then receive concomitant radiotherapy (RT) at a dose of 60Gy and chemotherapy with temozolomide (TMZ), 75 mg/m2, daily during RT. This will be followed by adjuvant TMZ dosed at 200 mg/m2 for 6 cycles. Subjects will be followed until disease progression with serial brain MRIs, and for survival up to 5 years. The non-resectable cohort will not opened due to limited product availability.

A Phase I study of neural stem cell based virotherapy in combination with standard radiation and chemotherapy for patients with newly diagnosed malignant glioma

Neural Stem Cell Based Virotherapy of Newly Diagnosed Malignant Glioma

Neural Stem Cell Oncolytic Adenoviral Virotherapy of Newly Diagnosed Malignant Glioma

Using a 3+3 dose escalation design, three to six patients were to be enrolled per dose in each of the 3 cohorts. If no patients in the cohort experienced a dose-limiting toxicity (DLT), then the next cohort enrolled a minimum of 3 patients. If one of three patients experienced a DLT, then 3 more patients were evaluated at that dose level. If none of these three additional patients experienced a DLT, then dose escalation occurs, unless this is the highest dose, in which case dose escalation is stopped and the highest dose is declared the MTD. If 1 or more of these additional 3 patients had a DLT, then three additional patients may be entered, after discussion with the sponsor, at the next lowest does level if only three patients were treated previously at that dose. If two or more patients experienced a DLT Dose escalation will be stopped; 3 more patients could be added with sponsor approval at the next lower dose level.

Per Response Assessment in Neuro-Oncology Criteria (RANO, 2017) for target lesions as assessed by MRI: Complete Response (CR): The enhancing tumor is no longer seen by neuroimaging; Partial Response (PR): Decrease of ≥ 50% in the product of two diameters with the patient on a stable or decreasing dose of steroids; Minor Response (MR): Decrease in diameter products of \< 50% with the patient on a stable or decreasing dose of steroids; Stable Disease (SD): The scan shows no change. Patients should be receiving stable or decreasing doses of steroids; Progression (P): Increase of \> 25% in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. A concomitant decrease in steroid dose will rule out a progression designation during the first two months after completion of radiation; Pseudoprogression (PP): Radiological changes without concomitant neurological changes.

National Cancer Institute (NCI)

Northwestern University

Professor and Chairman

Number of patients in each cohort affected by serious adverse events

Patients with resectable tumors underwent surgical resection followed by injection of neural stem cells loaded with the virus (0.5x10\^8 NSCs loading 6.25x10\^10 vp) and then received standard chemoradiotherapy.

Resectable Disease Cohort 1

Patients with resectable tumors underwent surgical resection followed by injection of neural stem cells loaded with the virus (.0x10\^8 NSCs loading 1.25x10\^11 vp) and then received standard chemoradiotherapy.

Resectable Disease Cohort 2

Patients with resectable tumors underwent surgical resection followed by injection of neural stem cells loaded with the virus (1.5x10\^8 NSCs loading 1.875x10\^11 vp) and then received standard chemoradiotherapy.

Resectable Disease Cohort 3

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus at dose level 0.5x10\^8 NSCs loading 6.25x10\^10 vp and then receive standard chemoradiotherapy.

Neural stem cells loaded with an oncolytic adenovirus: The primary objectives are to evaluate the safety of the combined therapy and determine the maximum tolerated dose (MTD) for a future Phase II study.

Arm B: Resectable Disease Cohort 1

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus at dose level 1.0x10\^8 NSCs loading 1.25x10\^11 vp and then receive standard chemoradiotherapy.

Neural stem cells loaded with an oncolytic adenovirus: The primary objectives are to evaluate the safety of the combined therapy and determine the maximum tolerated dose (MTD) for a future Phase II study.

Arm B: Resectable Disease Cohort 2

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus at dose level 1.5x10\^8 NSCs loading 1.875x10\^11 vp and then receive standard chemoradiotherapy.

Neural stem cells loaded with an oncolytic adenovirus: The primary objectives are to evaluate the safety of the combined therapy and determine the maximum tolerated dose (MTD) for a future Phase II study.

Arm B: Resectable Disease Cohort 3

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Christina Amidei, PhD

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus (dose: 0.5x10\^8/NSCs/6.25x10\^10 vp) and then receive standard chemoradiotherapy. No dose limiting toxicities were experienced in this cohort.

Arm B/Cohort 1

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus (dose: 1.0x10\^8 NSCs/1.25x10\^10 vp) and then receive standard chemoradiotherapy. No dose limiting toxicities were experienced in this cohort.

Arm B/Cohort 2

.5x10\^8 NSCs/1.875x10\^10 vp

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus (dose: 1.5x10\^8 NSCs/1.875x10\^10 vp) and then receive standard chemoradiotherapy. One dose limiting toxicity event was experienced in this cohort, prompting 3 additional patients being added to the cohort; no dose limiting toxicities were experienced in this addition to the cohort, and this dose was determined to be the MTD.

ArmB/Cohort 3

No screen failures were encountered and all 12 patients were evaluable.

Percentage of Dose-limiting Toxicities

Percentage of participants with tumor response: Partial

Percentage of participants with tumor response: Pseudoprogression

Percentage of participants with tumor response: Stable disease

Analyses were conducted for the entire cohort (N=12) for secondary objectives.

Total Cohort

Nine of 12 patients had measureable disease post-surgery and were followed with serial MRIs.

Assessment of Tumor Response.

Progression-free Survival

Overall Survival

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus and then receive standard chemoradiotherapy. The unresectable cohort was not able to be opened due to limited product availability.

Neural stem cells loaded with an oncolytic adenovirus: The primary objectives are to evaluate the safety of the combined therapy and determine the maximum tolerated dose (MTD) for a future Phase II study.

Resectable Disease

Cohort 1: 0.5x10^8/NSCs/6.25x10^10 vp

Cohort 2: 1.0x10^8 NSCs/1.25x10^10 vp

Cohort 3: 1.5x10^8 NSCs/1.875x10^10 vp

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Neoplasm Metastasis

Breast Neoplasms

Influenza, Human

Virus Diseases

Neoplastic Processes

Breast Diseases

Skin Diseases

10e7 PFU CodaLytic administered intratumorally once every 4 weeks (3 doses total)

10e7 PFU CodaLytic administered intratumorally once every 2 weeks (5 doses total)

10e8 PFU CodaLytic administered intratumorally once every 2 weeks (5 doses total)

CodaLytic is a virotherapeutic product based on the wild-type influenza strain A/California/07/2009

CodaLytic

The goal of this phase 1 open label clinical trial is to evaluate the safety and preliminary efficacy of CodaLytic, an intratumorally-administered oncolytic virus, in patients with metastatic or otherwise inoperable breast cancer.

The main questions it aims to answer are:

* How safe is CodaLytic when administered in escalating dosing groups into targeted lesions?
* What is the impact of CodaLytic on lesion response and disease progression?

Eligible participants will be enrolled into four (4) escalating dose groups and treated with Codalytic through injection into a selected lesion(s) over twelve (12) weeks and then followed for up to one (1) year after the first dose. A safety committee will review the safety profile of each dosing group before the next dose-escalation.

Study procedures will include physical examinations, injection site assessments, biopsies, imaging, and collection of blood/urine to assess safety, the body's immune response, and efficacy.

This study is a Phase 1, open-label, 3+3 dose-escalation, clinical trial to evaluate the safety and preliminary efficacy of CodaLytic in patients with metastatic or otherwise inoperable breast cancer.

After providing informed consent, screened participants will undergo baseline safety assessment and imaging. The Investigator will select an accessible lesion for intratumoral injection of CodaLytic (the injected lesion), and a core needle biopsy sample of this lesion will be obtained for eligible participants to be dosed. The Investigator will also select additional lesions for imaging (target lesions); these target lesions will not be injected or biopsied. If possible, another accessible lesion that is not a target lesion will be selected for biopsy to assess abscopal effect.

Three (3) eligible participants who meet all study inclusion and no exclusion criteria will be enrolled in each of four (4) escalating-dose cohorts and administered intratumoral CodaLytic. Up to 3 additional participants per cohort may be enrolled. During the dosing period, participants will be assessed for adverse events, serious adverse events, and dose-limiting toxicities. A safety review committee will review the safety data through Day 28 for the participants in Cohort 1 before participants are enrolled in Cohorts 2 and 3 and safety data through Day 28 for the participants in Cohorts 2 and 3 before participants are enrolled in Cohort 4. The safety review committee will also meet on an ad hoc basis to review any unexpected safety concerns.

Enrolled participants will be followed for adverse events, serious adverse events, dose-limiting toxicities to assess safety of CodaLytic administration. Biopsy samples of the injected lesion and, if possible, from a noninjected, nontarget lesion will be collected at Week 5. At the end of treatment, imaging will be performed for staging by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, and biopsy samples will be collected. Repeat disease assessment will be performed 4 to 8 weeks after the Month 3/EOT visit if complete response (CR) or partial response (PR) is observed at that visit or if progressive disease (PD) is seen at that visit and the participant has not begun additional cancer treatment. After the treatment period, participants may enroll in other studies or be managed with other treatment modalities as indicated, but follow-up assessments of Investigator-assessed tumor response and anticancer treatments will be recorded at Months 6 and 12.

Study participants eligible to participate will be enrolled in each of 4 escalating-dose cohorts and administered intratumoral CodaLytic in the injected lesion during the dosing period as follows: Three (3) doses 4 weeks apart at the low dose, five (5) doses 2 weeks apart at the low dose, three (3) doses 4 weeks apart at the high dose and five (5) doses 2 weeks apart at the high dose.

A Study of CodaLytic, an Intratumoral Oncolytic Virus, in Patients With Breast Cancer

Phase 1 Study of CodaLytic, an Intratumoral Influenza-based Oncolytic Virus, in Patients With Metastatic or Otherwise Inoperable Breast Cancer

To assess the frequency of Serious Adverse events (SAEs) of CodaLytic administered by intratumoral injection at 2-weekly or 4-weekly intervals at doses of 10e7 and 10e8 plaque-forming units (PFU)/mL

To assess the frequency of Adverse events (AEs) of CodaLytic administered by intratumoral injection at 2-weekly or 4-weekly intervals at doses of 10e7 and 10e8 plaque-forming units (PFU)/mL

To assess the frequency of Dose-limiting toxicities (DLTs) of CodaLytic administered by intratumoral injection at 2-weekly or 4-weekly intervals at doses of 10e7 and 10e8 plaque-forming units (PFU)/mL

To assess the Overall response rate (ORR) for CodaLytic intratumoral administration as a measurement of tumor response and disease progression

To assess the Duration of response (DoR) for CodaLytic intratumoral administration as a measurement of tumor response and disease progression

To assess the Disease control rate (DCR) for CodaLytic intratumoral administration as a measurement of tumor response and disease progression

To assess the Progression-free survival (PFS) for CodaLytic intratumoral administration as a measurement of tumor response and disease progression

Codagenix, Inc

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Recurrence

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Recombinant human adenovirus type 5: one lesion was selected for intratumoral injection.Intratumoral injection of H101 was performed on day 1 and day 4 of each cycle, and was repeated once every 3 weeks. H101 dose:

① Tumor maximum diameter ≤5cm, 1.5×10\^12vp (3 injections) on day 1, 1.0×10\^12vp (2 injections) on day 4.

② Tumor maximum diameter \>5cm but ≤10cm, 3.0×10\^12vp (6 injections) on day 1 and 2.0×10\^12vp (4 injections) on day 4.

③ Tumor maximum diameter \>10cm, 4.5×10\^12vp (9 injections) on day 1 and 3.0×10\^12vp (6 injections) on day 4.

H101 intratumoral injection until the tumor is completely regressed to stop the drug, but not more than 5 cycles at most.

Camrelizumab: administered after H101 on day 1 of each cycle and repeated for 3 weeks. Camrelizumab dose: 200 mg IV.

Recombinant human adenovirus type 5: one lesion was selected for intratumoral injection.Intratumoral injection of H101 was performed on day 1 and day 4 of each cycle, and was repeated once every 3 weeks. H101 dose:

① Tumor maximum diameter ≤5cm, 1.5×1012vp (3 injections) on day 1, 1.0×1012vp (2 injections) on day 4.

② Tumor maximum diameter \>5cm but ≤10cm, 3.0×1012vp (6 injections) on day 1 and 2.0×1012vp (4 injections) on day 4.

③ Tumor maximum diameter \>10cm, 4.5×1012vp (9 injections) on day 1 and 3.0×1012vp (6 injections) on day 4.

H101 intratumoral injection until the tumor is completely regressed to stop the drug, but not more than 5 cycles at most.

Camrelizumab: administered after H101 on day 1 of each cycle and repeated for 3 weeks. Camrelizumab dose: 200 mg IV.

Recombinant human adenovirus type 5＋Camrelizumab

Xiang Zhang

There is no standard treatment for recurrent cervical cancer that progresses or persists after first-line treatment. The objective response rate of anti-PD-1 antibody treatment is about 15%. The purpose of this study was to evaluate whether the regimen could improve the objective response rate by intratumoral injection of oncolytic virus(recombinant human adenovirus type 5 injection, H101) combined with anti-PD-1 antibody(camrelizumab).

1. Main research purpose To evaluate the efficacy of H101 combined with camrelizumab in patients with incurable recurrent cervical cancer.
2. Secondary research purpose To evaluate other curative effects of H101 combined with camrelizumab in patients with incurable recurrent cervical cancer.

   To evaluate the safety of H101 combined with camrelizumab in patients with incurable recurrent cervical cancer.
3. Purpose of Exploratory Research To explore the changes of tumor microenvironment before and after H101 injection and the mechanism of action in combination with PD-1, and to accurately screen the beneficiaries based on molecular expression.
4. Overall experimental design This study is a multicenter, prospective, clinical study to investigate the efficacy and safety of H101 combined with camrelizumab in the treatment of incurable recurrent cervical cancer patients. It is expected that 55 subjects will be enrolled.

   The study was divided into 5 phases: screening period, baseline period, treatment period, and follow-up period. Patients with recurrent cervical cancer who were eligible for inclusion and were incurable by previous first-line treatment were screened. During the follow-up period, follow-up was conducted every 1 month for at least 2 years.
5. Subject population The target population of this study was patients with recurrent cervical squamous cell carcinoma/adenocarcinoma/adenosquamous carcinoma who were incurable after first-line therapy.
6. Treatment allocation All subjects enrolled in this study received H101 combined with camrelizumab.
7. Drug dosage and administration in the trial Dosing regimen: H101 + camrelizumab. 1) H101: 1 lesion was selected for intratumoral injection. Intratumoral injection of H101 was used on the 1st and 4th day of each cycle, repeated once in 3 weeks. H101 dosage: Tumor maximum diameter ≤5 cm, 1.5×10\^12vp (3 injections) on day 1 and 1.0×10\^12vp (2 injections) on day 4.

Tumor maximum diameter \>5cm but ≤10cm, 3.0×10\^12vp (6 injections) on day 1, 2.0×10\^12vp (4 injections) on day 4.

Tumor maximum diameter \>10cm, 4.5×10\^12vp (9 injections) on day 1 and 3.0×10\^12vp (6 injections) on day 4.

H101 will be used until injected lesion disappears or 5 cycles, whichever occurs first.

2) Camrelizumab: 200 mg intravenously. Dosing after H101 on day 1 of each cycle, repeated 3 weeks. The drug was discontinued or discontinued for 2 years until the patient developed tumor progression or intolerable toxicity.

H101 Combined With Camrelizumab for Recurrent Cervical Cancer

Oncolytic Virus(H101) Combined With Camrelizumab for Recurrent Cervical Cancer: a Prospective, Multicenter Study

The proportion of CR(complete response) and PR(partial response) in all patients.

Refers to the time from the first treatment day to the first occurrence of disease progression or death from any cause (whichever occurs first), and the end point event is determined by the investigator according to RECIST v1.1.

The proportion of CR(complete response), PR(partial response) and SD(stable disease) in all patients.

Time between the date of randomization grouping and death from any cause or the end of the last follow-up visit.

Zhejiang Cancer Hospital

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Coxsackievirus Infections

1, 3 or 6 doses of CAVATAK (10\^9 TCID50) at 48 hour intervals.

CVA21

Stephen Ackland, MBBS FRACP

This study is designed to assess the safety and initial indications of efficacy resulting from multiple doses of CAVATAK injected directly into solid tumours of the Head and Neck that have been confirmed to express ICAM-1 and DAF.

CAVATAK (Coxsackievirus A21) is a naturally occurring common cold virus that preclinical research indicates can preferentially infect and kill cancer cells expressing the receptors ICAM-1 and/or DAF. This virus is known to cause self limiting upper respiratory infections and has been used previously to challenge therapies against the common cold. The virus is not generically modified.

The study proposes to administer CAVATAK to three cohorts each of three patients. The first cohort will receive a single dose, the second cohort will receive three doses, and the final cohort will receive six doses. There will a 48 hour interval between repeated doses.

The primary objective of the study is to determine the safety and efficacy of CVA21 given by intratumoural injection in the treatment of recurrent, unresectable squamous cell carcinoma of the head and neck by measuring primary and field tumour status and adverse effects.

Secondary objectives of the study are:

1. Indirect measurements of efficacy by measuring appropriate biomarkers in serum and tumour biopsy samples for viral replication, induction of apoptosis and anti-tumour immune responses.
2. To determine the time course of potential primary and secondary viraemia.
3. To characterise the time course of the anti-CVA21 antibody response after administration of CVA21

A Study of the Intratumoural Administration of CAVATAK to Head and Neck Cancer Patients (VLA-X06)

A Phase I, Open-label, Dosage Escalation, Study of Multiple Doses of CAVATAKTM (CVA21; Coxsackievirus A21) Administered Intratumourally in the Treatment of Squamous Cell Carcinoma of the Head and Neck Bearing ICAM-1 Receptors (VLA-X06)

Viralytics

Melanoma

Oncolytic virotherapy, intratumoral administrations of TBI-1401(HF10)

Patients will receive intratumoral administrations of TBI-1401(HF10). The dose is 1 mL of 1x10\^6 TCID50/mL.

TBI-1401(HF10)

Patients will receive intratumoral administrations of TBI-1401(HF10). The dose is 1 mL of 1x10\^7 TCID50/mL.

Naoya Yamazaki

The purpose of this study is to determine whether TBI-1401(HF10), a spontaneously attenuated mutant of Herpes Simplex Virus Type 1 (HSV-1), is safe and tolerable in the treatment of solid tumors with superficial lesions.

This is an open label, non-randomized, dose escalation Phase I study evaluating the repeated intratumoral administrations of the TBI-1401(HF10), a spontaneously attenuated mutant of HSV-1, in patients with solid tumors with superficial lesions (e.g., malignant melanoma and squamous cell carcinoma of the skin).

The study will evaluate the safety and tolerability of repeated intratumoral administrations of TBI-1401(HF10) at dose levels of 1 x 10\^6 TCID50/dose (cohort 1) and 1 x 10\^7 TCID50/dose (cohort 2) in Japanese patients. Three patients will be enrolled in each cohort. Patients in the each cohort will receive a total of four intratumoral administrations in the same lesion.

A Study of TBI-1401(HF10) in Patients With Solid Tumors With Superficial Lesions

A Phase I Study of Repeated Intratumoral Administration of TBI-1401(HF10), a Replication Competent HSV-1 Oncolytic Virus, in Patients With Solid Tumors With Superficial Lesions

Evaluation of cytokine profiles in serum by immunoassay.

Antitumor T-cell reactivity in serum will be evaluated by flow cytometry.

Treg population in serum will be evaluated by flow cytometry.

Core biopsies will be performed to evaluate the histopathological response with TBI-1401(HF10) administrated tumor.

Adverse events will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.0).

Overall tumor response will be evaluated by modified World Health Organization (mWHO) response criteria in the measurable target lesion(s) and unmeasurable/evaluable target lesion(s).

Anti-HSV-1 antibodies will be assessed in serum.

Takara Bio Inc.

Vaccinia

Communicable Diseases

Poxviridae Infections

DNA Virus Infections

Double Recombinant Vaccinia Virus VV-GMCSF-Lact

Intratumoral injections:

1\*107 PFU (calculated at minimal ED on mice); 2\*107 PFU; 4\*107 PFU; 6\*107 PFU; 8\*107 PFU; 10\*107 PFU;

Elena V. Kuligina, PhD

Vera S. Berezina, PhD

Petr V. Krivorotko, Professor

Purpose of the study is to evaluate the safety, tolerability and pharmacokinetic parameters of the drug based on double recombinant vaccinia virus VV-GMCSF-Lact, in patients with recurrent/refractory metastatic breast cancer in successive cohorts with dose escalation with single and multiple administration.

The study provides: determination of the maximum tolerated dose of the drug and the frequency, nature, intensity and duration of adverse events connected with the use of the study drug in escalating doses; detection of dose-limiting toxicity, its severity, duration and reversibility; determination of the profile of virus pharmacokinetics and antivirus antibodies; assessment of the objective response to the treatment.

Stage 1,: The virus drug is administered intratumorally once according to a "3+3" design in the dosage from 1\*107 PFU to 10\*107 PFU. The frequency of dose-limiting toxicity (DLT) will be evaluated (non-hematological toxicity III degree and above; development of febrile neutropenia and body temperature \> 38.3°C more than two days after drug administration; thrombocytopenia III degree and above and/or hemorrhagic complications; repeated increase in ALT and/or AST activity is more than 4 times higher than the normal upper limit).

Escalation to the next level occurs if there is no DLT in the entire cohort under study. The study stops if the incidence of DLT in a cohort of 3 patients is 2 or 3. The maximum tolerated dose (MTD) will be considered the studied dose that is lower than the dose which DLT was determined. Stage 1 assumes randomization of no more than 36 patients.

Stage 2, multiple administration: According to Stage 1 the study will move to the second stage if there will be possibility to study at least one dosage regimen based on the previously studied dose. At Stage 2 two doses in ascending order below the MTD and MTD are planned to be used. Escalation to the next level occurs if no DLT is observed during dosing of the first three patients. If DLT develops and drug administration is discontinued, the patient is not excluded from the study, her drug administration visits are skipped, and she goes through all follow-up visits. The drug will be administered intratumorally 1 time per week for 4 weeks in 3 dosages: MTD and 2 lower dosages. Each cohort will include up to 6 patients in a "3+3" design. It is expected to include up to 24 patients, taking into account the possible inclusion of patients to replace those who left.

Open Multi-cohort Study of Safety and Tolerability

Open Multi-cohort Study of the First Phase of Safety of a Drug Based on Double Recombinant Vaccinia Virus VV-GMCSF-Lact

Open Multi-cohort Study of the First Phase of Safety of a Drug Based on Double Recombinant Vaccinia Virus VV-GMCSF-Lact in Patients With Recurrent/Refractory Metastatic Breast Cancer With Single and Multiple Administration

Determination of the antivirus antibodies titer in the blood after 7, 14, 21, 28 days after intratumoral administration.

Assessment of Objective response (stabilization / progression rate) to treatment on the RECIST 1.1 scale.

Evaluation of tumor size according to the results of CT.

The severity of adverse events will be assessed according to CTCAE (Common Terminology Criteria for Adverse Events) Version 5.0. National Cancer Institute. 2017.

Degree of severity, duration and reversibility of dose-limiting toxicity will be detected

Determination of virus concentrations in blood after 5, 15, 30 minutes, 1, 3, 6, 12, 24, 48, 72, 120, 168 and 216 hours after intratumoral administration

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neural Stem Cell Based Virotherapy of Newly Diagnosed Malignant Glioma	NCT03072134	Glioma Anaplastic Astr... Anaplastic Olig... Anaplastic Olig... Glioblastoma Mu... Astrocytoma, Gr... Astrocytoma, Gr... Brain Cancer	Neural stem cel...	18 Years -	Northwestern University
A Study of CodaLytic, an Intratumoral Oncolytic Virus, in Patients With Breast Cancer	NCT05600582	Breast Neoplasm... Neoplasm Metast...	CodaLytic	18 Years -	Codagenix, Inc
H101 Combined With Camrelizumab for Recurrent Cervical Cancer	NCT05234905	Uterine Cervica... Oncolytic Virot... Camrelizumab	Recombinant hum...	18 Years - 80 Years	Zhejiang Cancer Hospital
A Study of the Intratumoural Administration of CAVATAK to Head and Neck Cancer Patients (VLA-X06)	NCT00832559	Head and Neck C...	CVA21	18 Years -	Viralytics
A Study of TBI-1401(HF10) in Patients With Solid Tumors With Superficial Lesions	NCT02428036	Solid Tumor	TBI-1401(HF10) TBI-1401(HF10)	20 Years -	Takara Bio Inc.
Open Multi-cohort Study of the First Phase of Safety of a Drug Based on Double Recombinant Vaccinia Virus VV-GMCSF-Lact	NCT05376527	Oncolytic Virot...	Double Recombin...	18 Years -	"Oncostar" LLC
A Study of TBI-1401(HF10) in Patients With Solid Tumors With Superficial Lesions	NCT02428036	Solid Tumor	TBI-1401(HF10) TBI-1401(HF10)	20 Years -	Takara Bio Inc.

Spots Global Cancer Trial Database for oncolytic virotherapy