A Single-Arm, Open-Label, Investigator-Initiated Clinical Trial to Evaluate the Safety, Tolerability and Efficacy of Oncolytic Virus Injection (OVV-01) in Combination With IBR900 Cell Injection in Patients With Advanced Malignant Tumors
Overview
- Phase
- Early Phase 1
- Intervention
- Not specified
- Conditions
- Advanced Solid Tumor
- Sponsor
- Beijing Boren Hospital
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Dose limiting toxicity (DLT)
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a prospective, multi-center, open-label, single-arm, investigator-initiated clinical trial to evaluate the safety and efficacy of oncolytic virus injection (OVV-01) in combination with trained immunity NK (tiNK) cell injection (IBR900) for patients with advanced malignant tumors.
Detailed Description
In this study, it is planned to enroll about 6-12 subjects with advanced solid tumors or relapsed/refractory lymphomas who have failed in the third-line or higher standard of care in about 1-3 study sites in China. A 2-dose gradient joint exploratory study using the traditional "3+3" mode is adopted in this study. If the high-dose group does not yet reach the MTD, the investigator and funder will decide whether to continue the dose escalation and whether to add a new dose group. 2 dose gradients are used for the OVV-01 injection, and the total infusion dose of IBR900 cell injection is 4.0×10\^9 cells per cycle. OVV-01 injection will be first administered at W1D1 and then at W4D1 followed by every 2 weeks as a treatment cycle, for a total of 6 doses; after the test in the high-dose group is completed, the investigator and sponsor will determine whether to adjust the dosing frequency of OVV-01 (such as once a week) based on the result evaluations. The IBR900 cell injection will be first administered at W1D3 and W1D5 for 2 infusions, and then at W4D3 and W4D5, followed by every 4 weeks as a cycle, for a total of 4 doses, and cell infusions will be conducted at W1, W4, W8 and W12, respectively.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects who are ≥18 years old and ≤75 years old, male or female;
- •Subjects with advanced malignant tumors with the primary lesions and/or metastatic lesions diagnosed by histopathology/cytological examinations, including but not limited to: melanoma, the head and neck squamous cell carcinoma, cervical carcinoma, osteosarcoma, nasopharyngeal carcinoma, breast carcinoma, lung carcinoma, colorectal carcinoma, liver carcinoma, gastric carcinoma, lymphoma, etc.;
- •Subjects with solid tumors or relapsed/refractory lymphomas who have failed in the third-line or higher standard of care;
- •Subjects with at least one measurable lesion (non-lymph node lesion with longest diameter ≥10 mm, or lymph node lesion with short diameter ≥15 mm) according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Evaluation Criteria for Efficacy of Lymphoma Lugano 2014;
- •Subjects with the Eastern Cooperative Oncology Organization (ECOG) score of 0-2;
- •Subjects with the expected survival ≥ 3 months;
- •Subjects with adequate bone marrow function:
- •White blood cell (WBC)≥3.0×10\^9/L;
- •Neutrophils (ANC)≥1.5×10\^9/L (cannot use the colony stimulating factor within 3 days before the test);
- •Lymphocyte count ≥6.0×10\^8/L;
Exclusion Criteria
- •Subjects without measurable lesions;
- •Subjects with symptomatic brain metastases (but subjects who have asymptomatic brain metastases or have been clinically stable for more than 3 months with local treatment can be included in the study);
- •Subjects who have received radiotherapy for the target lesion within 2 months;
- •Subjects with other active malignant tumors that require simultaneous treatment;
- •Subjects who are known to be allergic to the study drug or its active ingredients and excipients;
- •Subjects who have received or been receiving or still need to receive other investigational drug or antiviral treatments within 4 weeks before administration;
- •Subjects who are going to undergo or have received tissue/organ transplantation;
- •Subjects who have active infections or fever \>38.5°C of unknown cause during the screening phase and before the first dose;
- •Subjects with active tuberculosis (TB) who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening;
- •Subjects who are positive in the treponema pallidum serology test;
Outcomes
Primary Outcomes
Dose limiting toxicity (DLT)
Time Frame: 7 weeks after initial administration
To evaluate the safety and tolerability of OVV-01 injection and IBR900 cell injection
Adverse events (AEs)
Time Frame: 24 weeks after initial administration
The incidence and severity of AEs assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and the correlation between AEs and OVV-01 injection combined with IBR900 cell injection
Secondary Outcomes
- Progression-free survival (PFS)(Up to 1 year after administration)
- Duration of overall response (DOR)(Up to 1 year after administration)
- Plasma concentration of anti-VSV-G antibody and neutralizing antibody(16 weeks after initial administration)
- Objective response rate (ORR)(Up to 1 year after administration)
- Peak plasma concentration of IBR900 cells(16 days after initial administration)
- Overall survival (OS)(Up to 1 year after administration)
- Disease control rate (DCR)(Up to 1 year after administration)
- Peak plasma concentration of OVV-01(14 days after the last administration)