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
Phase: PHASE1
Conditions: Oncolytic Virotherapy
Sponsor: "Oncostar" LLC

Study OƯicial Title: 
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 
Study NCT Number: 
NCT05376527 
Document Date: 
12-MAR-2026 

_________________________________________________________________________________ 
LLC «ONCOSTAR»  
Moscow, Territory of the Skolkovo Innovation Center,  
Bolshoy Boulevard, 42, bldg. 1 
Tel: +7 913 986 35 52 
___________________________________________________________________________ 
To: ClinicalTrials.gov PRS Review Team 
Date: 2026-03-12 
Re: Protocol and SAP Submission for Study NCT05376527 / Oncolact2020 
Subject: Clarification regarding the English versions of the Protocol and Statistical 
Analysis Plan 
 
Dear PRS Review Team, 
This letter is provided in response to the request for the English translation of the Protocol and 
the Statistical Analysis Plan (SAP) for the clinical study NCT05376527 / Oncolact2020. 
The study is a local multicenter clinical trial conducted exclusively within the Russian 
Federation under the jurisdiction of the Ministry of Health of the Russian Federation. 
Consequently, the official versions of the Protocol and SAP were developed and approved by the 
National Regulatory Authority and the National Ethics Committee in the Russian language only. 
To ensure transparency and fulfill the requirements of ClinicalTrials.gov, we are providing below 
an Extensive Integrated Summary of the Protocol and the Statistical Analysis Plan in English. 
This summary contains all essential technical and statistical information required for the 
scientific evaluation of the study design and results. 
1. Key Protocol Information (Oncolact2020) 
• 
Study Design: An open-label, multi-center, multi-cohort Phase I study utilizing a dose-
escalation design to evaluate the safety, tolerability, and pharmacokinetics of the 
investigational product. 
• 
Investigational Product: VV-GMCSF-Lact (recombinant vaccinia virus strain), solution 
for injection, 2 х 107 PFU/mL. 
• 
Target Population: Patients with recurrent and/or refractory metastatic breast cancer 
who have exhausted standard-of-care treatment options. 

• 
Dosing Regimen: The study involves both single and multiple intratumor administrations 
across sequential dose-escalation cohorts. 
• 
Objectives: 
o Determination of the maximum tolerable dose of the drug; 
o Determination of the frequency, nature, intensity, and duration of adverse 
reactions associated with the use of the investigational drug when taken in 
increasing doses; 
o Identification of dose-limiting toxicity, its severity, duration, and reversibility; 
o Determining the pharmacokinetic profile of the virus and antibodies to it; 
o Evaluating the objective response to the treatment; 
o Evaluating the dynamics of changes in tumor size. 
2. Statistical Analysis Plan (SAP) Summary 
• 
Sample Size Justification: As a Phase I dose-escalation study, the sample size is 
determined by the number of dose cohorts and the observed toxicities (3+3 design or 
similar), rather than a formal power calculation for efficacy. This study will not test 
statistical hypotheses, so no formal justification of the sample size is required. 
It is estimated that up to 73 patients may be enrolled and screened, taking into account 
possible screening failures (up to 15 patients), up to 58 patients will receive the study 
drug, and no more than 54 patients will complete the study according to the protocol, 
with additional patients recruited at each stage and taking into account the possible 
inclusion of patients to replace those who drop out (no more than 4 patients in total in 
both stages). 
• 
Analysis Sets: 
o Intent-to-Treat: The ITT dataset includes all subjects who received the study 
drug, regardless of their degree of adherence to the protocol during the study. This 
dataset is the primary dataset for analysis and will be used to evaluate all planned 
endpoints. 
o Per Protocol: All planned endpoints will be analyzed (in addition to the ITT 
analysis) using a data set of study participants selected according to the protocol 
(PP). A participant will be excluded from the PP data set in the following cases: 
• 
The patient's refusal to continue participating in the study. 
• 
Incorrect inclusion (i.e., non-compliance with the inclusion/exclusion 
criteria identified during the study). 
• 
Failure of the subject to comply with the rules of participation in the study. 
• 
The emergence of reasons/situations during the study that threaten the 
patient's safety (e.g., serious adverse reactions, detection of pregnancy in 
the patient).  
• 
The development of conditions in the patient described in the exclusion 
criteria. 
• 
The need to use drugs or therapies not permitted by the protocol during the 
study. 
• 
The patient is diagnosed with COVID-19. 

o Safety Population: All patients received at least one dose of VV-GMCSF-Lact. 
This is the primary set for all safety and tolerability analyses. 
o Pharmacokinetic (PK) Population: All patients who received the study drug and 
provided sufficient blood/biological samples for viral DNA/titer determination. 
o Full Analysis Set (FAS): Used for the assessment of preliminary efficacy (ORR, 
DCR) in patients with at least one post-baseline tumor assessment. 
o PK set: The analysis of pharmacokinetic and pharmacodynamic parameters will 
include data obtained from all patients who received the study drug, including 
those who withdrew early. 
• 
Statistical Methodology: 
o Safety: Descriptive statistics for Adverse Events (AEs), coded via MedDRA, and 
laboratory abnormalities. 
o PK: A statistical plan for analyzing pharmacokinetic/pharmacodynamic data will 
be developed based on the actual values of virus concentration in the blood of 
patients. The statistical model will consider data from preclinical studies and the 
results of pharmacokinetic/pharmacodynamic evaluations of similar drugs. Based 
on the results of the development, a statistician will select and test a function 
describing the virus replication process over time, determining the replication 
coefficients and replication rate. The model will be constructed using a suitable 
software package (e.g., SAS). The developed model will be used to evaluate the 
entire set of data obtained, as well as individual patient data. 
o Efficacy: Efficacy parameters will be determined at Visits 10-12 in the first phase 
and Visits 6, 10, 11, 12 in the second phase based on computed tomography data. 
Objective response (rate of stabilization/progression) to treatment. 
The effectiveness of the treatment will be assessed using the RECIST 1.1 scale. 
The primary endpoint analysis will be performed by estimating the response rates 
with 95% CI for both the entire study population and all cohorts at all visits 
mentioned in this section for each phase. 
• 
Handling of Missing Data: 
o Before performing statistical analysis, the database will be checked for missing, 
questionable, and non-analyzable data. All such data will be collected and 
forwarded to the researcher for verification and/or possible correction prior to 
finalizing the statistical report and database. 
In this study, there are no plans to replace missing data subject to statistical 
analysis. 
In the case of an incomplete date, the following replacement will be made: 
• 
if the day is missing, the date will be adjusted to the 15th day of the 
corresponding month and year (e.g., 02.2023 will be adjusted to 15.02.2023) 
• 
if the day and month are missing, the date will be adjusted to 01.07 of the 
corresponding year. 
 
3. Commitment to Transparency 
We confirm that the information provided in this summary is fully consistent with the original 
Russian-language Protocol ver. 2.2 of 13.03.2024 and SAP ver. 2.0 of 23.01.2025. Should a full