NCT05376527

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

Completed Phase 1 Last updated 24 March 2025

What this trial tests

Phase 1 trial testing Double Recombinant Vaccinia Virus VV-GMCSF-Lact in Oncolytic Virotherapy in 34 participants. Completed in 27 February 2025.

Timeline

11 May 2022

Primary endpoint
27 February 2025

27 February 2025

Quick facts

Lead sponsor	"Oncostar" LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	34
Start date	11 May 2022
Primary completion	27 February 2025
Estimated completion	27 February 2025
Sites	1 location across Russia

Drugs / interventions tested

• Double Recombinant Vaccinia Virus VV-GMCSF-Lact — full drug profile →

Conditions studied

• Oncolytic Virotherapy — all drugs for Oncolytic Virotherapy →

Sponsor

"Oncostar" LLC — full company profile →

Who can join

18 and older, female only, with Oncolytic Virotherapy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current clinical landscape of oncolytic viruses as novel cancer immunotherapeutic and recent preclinical advancements.
   Yun CO, Hong J, Yoon AR. · · 2022 · cited 45× · PMID 36091031 · DOI 10.3389/fimmu.2022.953410
2. Oncolytic vaccinia virus and cancer immunotherapy.
   Xu L, Sun H, Lemoine NR, Xuan Y, et al · · 2023 · cited 36× · PMID 38283361 · DOI 10.3389/fimmu.2023.1324744
3. Recent progress in combination therapy of oncolytic vaccinia virus.
   Mirbahari SN, Da Silva M, Zúñiga AIM, Kooshki Zamani N, et al · · 2024 · cited 25× · PMID 38558795 · DOI 10.3389/fimmu.2024.1272351
4. Intratumoral delivery of immunotherapy to treat breast cancer: current development in clinical and preclinical studies.
   Mantooth SM, Abdou Y, Saez-Ibañez AR, Upadhaya S, et al · · 2024 · cited 13× · PMID 38803496 · DOI 10.3389/fimmu.2024.1385484
5. The Recombinant Oncolytic Virus VV-GMCSF-Lact and Chemotherapy Drugs against Human Glioma.
   Vasileva N, Ageenko A, Byvakina A, Sen'kova A, et al · · 2024 · cited 6× · PMID 38673835 · DOI 10.3390/ijms25084244
6. Microorganisms and Breast Cancer: An In-Depth Analysis of Clinical Studies.
   Naderi N, Mosahebi A, Williams NR. · · 2023 · cited 2× · PMID 38276152 · DOI 10.3390/pathogens13010006
7. Transcriptome Changes in Glioma Cells upon Infection with the Oncolytic Virus VV-GMCSF-Lact.
   Semenov DV, Vasileva NS, Dymova MA, Mishinov SV, et al · · 2023 · cited 2× · PMID 37998351 · DOI 10.3390/cells12222616
8. Characterizing Aptamer Interaction with the Oncolytic Virus VV-GMCSF-Lact.
   Dymova MA, Malysheva DO, Popova VK, Dmitrienko EV, et al · · 2024 · cited 1× · PMID 38398600 · DOI 10.3390/molecules29040848