A Clinical Study on Evaluating Intravenous Administration of IDOV-SAFE
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorPeking University
About this trial
Subjects were Chinese patients with histologically or cytologically confirmed advanced malignant solid tumors (mainly focused on MSS type colon and rectal cancer) who had failed standard systemic therapy and were inoperable.
The first stage was the dose escalation stage, which was divided into 4 dose groups according to the "3+3" dose escalation principle. One patient was enrolled in the first dose group, and 3-6 patients were enrolled in each of the latter three dose groups, with a total of 10-19 patients enrolled.
The second stage is the security extension stage, which is selected by SMC 1-2 dose cohorts were expanded for safety and divided into three cohorts in total(IIA, IIB, IIC) to explore the safety of sequential or combined administration modes with immune targeted therapy. Each cohort included 6-12 subjects at different dose levels, and three cohorts could be carried out at the same time.
The third stage is the dose expansion stage. According to the safety, PK and clinical data of the three cohorts in the second stage, 1-2 cohorts were selected by SMC for dose expansion. The sample size of each cohort was expanded to 20 cases on the original basis. The estimated ORR of the trial drug was 24%, and the ORR of the standard treatment was 5%. When the type I error was one-sided 0.025, and the power was 80%, the sample size was estimated by the normal approximation method. So each dose expansion phase A minimum of 20 subjects were required to be enrolled in the cohort.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Be fully aware of this study and voluntarily sign ICF.
Age range from 18 to 70 years old at the time of screening, gender is not limited.
At the time of screening, patients with advanced malignant digestive system tumors confirmed by histology or cytology, including MSS type colorectal cancer, bile duct cancer, stomach cancer, esophageal cancer, liver cancer, etc.
At the time of screening, the disease has progressed after or during standard treatment; Subjects with advanced malignant digestive system tumors with no standard treatment currently available, intolerance to chemotherapy, or greater than or equal to progression after 2-line system therapy.
Disqualifiers
At the time of screening, advanced malignant tumors have a chance of being cured by radical treatment.
Asymptomatic brain metastases such as untreated ones at the time of screening; Subjects with symptomatic central nervous system (CNS) metastatic or cancerous meningitis; Or there was other evidence of uncontrolled central nervous system or meningeal metastases in subjects who were judged by the investigator to be unsuitable for enrollment.
Prior to enrollment, there was severe chronic or active infection: active hepatitis B (HbsAg positive, HBV DNA test value greater than the upper limit of normal); Active hepatitis C (those with positive anti-HCV antibodies are further tested positive for HCV RNA); A known history of immunodeficiency virus (HIV) disease or a positive HIV antibody test; Other conditions requiring systemic anti-infective treatment in the 4 weeks prior to initial use of the investigational drug include, but are not limited to, hospitalization for infectious complications, bacteremia, severe pneumonia, or active tuberculosis.
At the time of screening, patients had a history of active autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc., or were receiving long-term systemic steroids (prednisone >10mg/ day or equivalent doses of the same drug) or any other form of immunosuppressant therapy within 14 days prior to the first use of the study drug.
Trial design
Design model
Parallel
Treatments tested in this trial
IIA1：1E9 PFU of oncolytic virus, sequentially combination
Biological/VaccineIntravenous injection of 1E9 PFU oncolytic virus, following disease progression on IDOV-SAFETM monotherapy, combination therapy with IDOV-SAFETM, toripalimab, and fruquintinib was administered.
IIA2：3E9 PFU of oncolytic virus, sequentially combination
Biological/VaccineIntravenous injection of 3E9 PFU oncolytic virus, following disease progression on IDOV-SAFETM monotherapy, combination therapy with IDOV-SAFETM, toripalimab, and fruquintinib was administered.
IIC1：1E9 PFU of oncolytic virus, early combination
Biological/VaccineIntravenous injection of 1E9 PFU oncolytic virus, following treatment with IDOV-SAFETM, subjects received combination therapy with IDOV-SAFETM, toripalimab, and fruquintinib starting from cycle 2 or cycle 3.
IIC2：3E9 PFU of oncolytic virus, early combination
Biological/VaccineIntravenous injection of 3E9 PFU oncolytic virus, following treatment with IDOV-SAFETM, subjects received combination therapy with IDOV-SAFETM, toripalimab, and fruquintinib starting from cycle 2 or cycle 3.
IID：3E9 PFU of oncolytic virus, Immuno-Oncology free combination
Biological/VaccineAfter one cycle of IDOV-SAFETM treatment of 3E9 PFU, subjects received combination therapy with IDOV-SAFETM and fruquintinib starting from cycle 2.
IIB：Other Gastrointestinal tumors
Biological/Vaccinecombination therapy with IDOV-SAFE + Toripalimab + Fruquintinib after progression on IDOV-SAFETM monotherapy.
Treatment groups
89 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: IIA1：1E9 PFU of oncolytic virus, sequentially combinationExperimental treatment 1 intervention
Group B: IIA2：3E9 PFU of oncolytic virus, sequentially combinationExperimental treatment 1 intervention
Group C: IIC1：1E9 PFU of oncolytic virus, early combinationExperimental treatment 1 intervention
Group D: IIC2：3E9 PFU of oncolytic virus, early combinationExperimental treatment 1 intervention
Group E: IID：3E9 PFU of oncolytic virus, Immuno-Oncology free combinationExperimental treatment 1 intervention
Group F: IIB：Other Gastrointestinal tumorsExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Occurrence of dose-limiting toxicity (DLT)
Occurrence of dose-limiting toxicity (DLT) on dose escalation phase
Time frame
21 days after the administration, up to 2 months2
Incidence of adverse events (AE)
Incidence of adverse events (AE) in monotherapy and combination phase
Time frame
After the subject completed the study, about 1 year3
The objective response rate (ORR) from baseline (data on screenning) for IDOV-Safe under three different combination regimens.
The objective response rate (ORR) from baseline (data on screenment) for IDOV-Safe under three different combination regimens.
Time frame
After subject complete tumor assessment, about half a yearSecondary outcomes
1
The level of (non-essential) viral DNA in tumor tissue
The investigator will select the subjects suitable for tumor tissue sample collection, with their informed consent.
Time frame
After the subject completed the treatment, about 1 year2
Tumor markers
Tumor marker test was performed every 6 weeks during screening and continued treatment
Time frame
Every 6 weeks during screening and continued treatment, about 1 year3
Anti-vaccinia virus neutralizing antibody test(VV-Nab)
Peripheral blood samples were collected for vaccinia virus neutralizing antibody (VV-Nab) detection at 0h (-60min) before the first dose on D1 and on D7 ± 1d after the first dose on D1. For subsequent cycles, samples were only collected at 0h (-60min) before the dose on D1.
Time frame
After the subject completed the treatment, about 1 year4
Levels of viral DNA in blood
During the dose escalation phase, expansion phase and dose expansion phase, peripheral blood samples were collected at 25 time points: 2 hours before each injection of D1, D3 and D5, and 30 minutes ± 5 minutes, 2 hours ± 15 minutes, 4 hours ± 30 minutes, 8 hours ± 1 hour, 12 hours ± 1 hour, 24 hours ± 1 hour, 36 hours ± 2 hours after each injection, as well as 48 hours ± 2 hours after the last injection of D5. In the second and third cycles, peripheral blood samples were collected at 6 time points: 2 hours before each injection of D1 and 30 minutes ± 5 minutes, 2 hours ± 15 minutes, 8 hours ± 1 hour, 12 hours ± 1 hour, 24 hours ± 1 hour after each injection. In the second and third cycles, peripheral blood samples were collected at 2 time points: 2 hours before each injection of D3 and D5 and 30 minutes ± 5 minutes after each injection. Viral DNA and live virus load were measured in all samples, and the half-life was calculated.
Time frame
After the subject completed the treatment, about 1 yearOther outcomes
1
Exploratory endpoint
Dynamic changes in biomarkers (e.g., CD4, CD8, PD-L1) in tissue specimens monitored before and after treatment.
Time frame
After the subject completed the study, about 1 year2
Exploratory endpoint
Single-cell/spatial transcriptomic/TCR sequencing was utilized to investigate changes in the tumor microenvironment and peripheral blood immune profiles.
Time frame
After the subject completed the study, about 1 yearSponsors and contacts
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Source ClinicalTrials.gov