Phase I Study of In Vivo CAR-Tumor Technology for the Treatment of Advanced Malignant Tumors

A Phase I Platform Study on the Treatment of Advanced Malignant Tumors Using In Vivo CAR-Tumor Technology

This study is a single-arm, open-label, dose-escalation platform clinical trial designed to evaluate the safety, tolerability, efficacy, pharmacokinetic and pharmacodynamic characteristics of CAR-Tumour oncolytic virus as a vector platform for the treatment of advanced malignant tumours.

Subjects will be screened and assigned to cohorts based on target and indication:

Cohort A: Intratumoural injection or intravenous injection of CAR-Tumor05 solution for the treatment of advanced malignant solid tumours Co-group B: Intratumoural injection, intravenous injection, subcutaneous injection, intramuscular injection, pleural perfusion, and intraperitoneal perfusion of CAR-Tumor05 injection for the treatment of advanced malignant solid tumours Co-group C: Intratumoural injection, intravenous injection, subcutaneous injection, intramuscular injection, pleural perfusion, and intraperitoneal perfusion of CAR-Tumor M01 injection for the treatment of advanced malignant solid tumours

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Biological: CAR-Tumor05; Biological: CAR-Tumor 05; Biological: CAR-Tumor M01

Detailed Description

This study is a single-arm, open-label, dose-escalation platform clinical trial designed to evaluate the safety, tolerability, efficacy, pharmacokinetic and pharmacodynamic characteristics of CAR-Tumour oncolytic virus as a vector platform for the treatment of advanced malignant tumours.

Dose escalation and subject enrolment principles

Dose Escalation Protocol:

This study employs a 3+3 design to identify the Maximum Tolerated Dose (MTD), and based on the MTD determination, the Recommended Phase 2 Dose (RP2D) will be established. A total of two dose groups are established.

In the initial Dose Group 1, following the first administration to the first subject, a 21-day DLT observation period will commence. If no DLT occurs during this period, the next two subjects at this dose level will be enrolled and receive their first administration, followed by a similar 21-day DLT observation period.

From dose level 2 onwards, there will also be a 21-day interval between the enrolment of the first and second subjects, who will then receive treatment at the corresponding dose level. Following the first administration, subjects will enter a 21-day DLT observation period; if no DLT occurs, further subjects at this dose level will be enrolled.

Subjects will be screened and assigned to cohorts based on target and indication:

Cohort A: Intratumoural injection or intravenous injection of CAR-Tumor05 solution for the treatment of advanced malignant solid tumours Co-group B: Intratumoural injection, intravenous injection, subcutaneous injection, intramuscular injection, pleural perfusion, and intraperitoneal perfusion of CAR-Tumor05 injection for the treatment of advanced malignant solid tumours Co-group C: Intratumoural injection, intravenous injection, subcutaneous injection, intramuscular injection, pleural perfusion, and intraperitoneal perfusion of CAR-Tumor M01 injection for the treatment of advanced malignant solid tumours

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yanjie Han; Phone Number: 01087788165; Email: annyhan_1997@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences 17 Panjiayuan Nanli, Chaoyang District

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Voluntarily sign the informed consent form, understand the study, agree to comply with the protocol, and agree to complete all trial procedures;
2. Be aged 18 years or over at the time of signing the informed consent form; gender is not restricted.
3. Patients with advanced solid tumours confirmed by histological and/or cytological examination of the primary and/or metastatic lesions.
4. Patients who have failed standard treatment, are at the end of standard treatment options, or are unsuitable for standard treatment for medical reasons.
5. Participants with an ECOG performance status score of 0-2 and an expected survival of at least 12 weeks.
6. Adequate organ and haematopoietic function: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count ≥ 75 × 10⁹/L (no platelet transfusions or thrombopoietin (TPO) therapy within 2 weeks prior to the first dose); haemoglobin ≥ 90 g/L (no blood transfusions within 2 weeks); Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or endogenous creatinine clearance (CCr) ≥ 50 mL/min; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN; in patients with liver metastases, AST and ALT < 5 × ULN; total serum bilirubin (TBIL) ≤ 2 × ULN; International Normalised Ratio (INR) ≤ 1.5 × ULN, or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;
7. Women of childbearing potential must undergo a pregnancy test within 7 days prior to the start of treatment, with a negative result.
8. Male and female subjects of childbearing potential must agree to use reliable contraception during the trial and for at least 6 months following the last dose.

Exclusion Criteria:

1. Subjects who have had other active malignant tumours within the past 5 years. Excluded are subjects who have been completely cured and do not require follow-up treatment, and subjects whose malignant tumours fall within the scope of the indication;
2. The longest diameter of the lesion to be injected is >100 mm;
3. Subjects who have participated in or are currently participating in clinical trials of other drugs or medical devices within the past 4 weeks;
4. Subjects who are scheduled to undergo or have previously undergone a tissue/organ transplant;
5. Subjects with human immunodeficiency virus (HIV) infection who have had AIDS-related opportunistic infections within the past 12 months, or whose CD4+ T-cell (CD4+) count is < 350 cells/μL; Patients who are positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) during the screening period, and whose HBV-DNA is above the lower limit of detection; patients who are positive for HCV antibody during the screening period and whose HCV-RNA is above the lower limit of detection; subjects with a positive serological reaction for Treponema pallidum;
6. Subjects who require antiviral medication during the study period or who are within 5 half-lives of antiviral medication at the time of the first dose.
7. Subjects who require therapeutic anticoagulants during the study period.
8. Subjects with uncontrolled active infections of grade ≥3 according to CTCAE V6.0 that are clinically significant;
9. Recipients who have received anticancer drug therapy, including chemotherapy, radiotherapy, biological therapy, endocrine therapy or immunotherapy, within 4 weeks prior to the first dose; recipients who have received small-molecule targeted therapy or oral fluoropyrimidine agents within 2 weeks prior to the first dose or within 5 half-lives (whichever is longer); Received traditional Chinese herbal medicines or proprietary Chinese medicines with anti-tumour indications within 2 weeks prior to the first dose; received nitrosoureas or mitomycin C within 6 weeks prior to the first dose; palliative radiotherapy for non-target lesions is permitted (≥2 weeks prior to the first dose);
10. Hypertension or pulmonary arterial hypertension uncontrolled by medication, or unstable angina; myocardial infarction or bypass or stent surgery within 6 months prior to dosing; history of chronic heart failure classified as New York Heart Association (NYHA) Class 3-4; Severe arrhythmias requiring treatment (excluding atrial fibrillation or paroxysmal supraventricular tachycardia deemed by the investigator to have no impact on the trial), including QTcF ≥450 ms in males and ≥470 ms in females (calculated using the Fridericia formula); cerebrovascular accident (CVA) or transient ischaemic attack (TIA) within 6 months prior to enrolment;
11. Patients with active autoimmune diseases or a history of autoimmune diseases that may recur; however, patients with the following conditions are not excluded and may be further screened: type 1 diabetes; hypothyroidism (if controlled by hormone replacement therapy alone); well-controlled coeliac disease; skin conditions not requiring systemic treatment (e.g. vitiligo, psoriasis, alopecia); any other condition that will not recur in the absence of external triggers;
12. Subjects who require systemic corticosteroids (>10 mg/day prednisolone or equivalent dose) or other immunosuppressive agents within 14 days prior to the first dose or during the study, with the following exceptions: adrenal replacement steroids (prednisolone ≤10 mg/day or equivalent dose of a similar agent); Topical, ophthalmic, intra-articular, intranasal or inhaled corticosteroids; prophylactic short-term (≤7 days) use of corticosteroids (e.g., for contrast medium allergy) or for the treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by contact allergens);
13. Subjects who are scheduled to receive any live vaccine during the screening or treatment periods;
14. Subjects with hypersensitivity to any component of the study drug, immunotherapy or related medications;
15. Subjects with psychiatric disorders, alcoholism, inability to quit smoking, drug addiction or substance abuse;
16. Pregnant or breastfeeding women;
17. Adverse reactions from previous anticancer treatment have not yet resolved to Grade 1 (CTCAE 5.0) (excluding alopecia);
18. The investigator determines that the subject has a serious uncontrolled medical condition, or other circumstances that may affect their ability to receive treatment in this study, and deems them unsuitable for participation;
19. Other circumstances deemed by the investigator to render the subject unsuitable for enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Intratumoural and intravenous administration of CAR-Tumor05 for the treatment of advanced malignant solid tumours，Two dose groups were established: 6 × 10⁹ PFU/mL and 6 × 10¹⁰ PFU/mL. Administration took place on day 1 (D1) of each cycle, with each treatment cycle lasting two weeks; a maximum of six cycles were administered, with multiple doses administered on the same day.	Biological: CAR-Tumor05; Intralesional injection, intravenous injection
Experimental: Group B; Intratumoural injection, intravenous injection, subcutaneous injection, intramuscular injection, pleural perfusion and intraperitoneal perfusion of CAR-Tumor05 injection for the treatment of advanced malignant solid tumours，Two dose groups were established: 6 × 10⁹ PFU/mL and 6 × 10¹⁰ PFU/mL. Administration took place on day 1 (D1) of each cycle, with each treatment cycle lasting two weeks; a maximum of six cycles were administered, with multiple doses administered on the same day.	Biological: CAR-Tumor 05; Intralesional injection, intravenous injection, subcutaneous injection, intramuscular injection, pleural perfusion, intraperitoneal perfusion
Experimental: Group C; Intratumoural injection, intravenous injection, subcutaneous injection, intramuscular injection, pleural perfusion and intraperitoneal perfusion of CAR-Tumor M01 injection for the treatment of advanced malignant solid tumours，Two dose groups were established: 6 × 10⁶ PFU/mL and 6 × 10¹¹ PFU/mL. Administration took place on day 1 (D1) of each cycle, with each treatment cycle lasting two weeks; a maximum of six cycles were administered, with multiple administration routes administered on the same day.	Biological: CAR-Tumor M01; Intralesional injection, intravenous injection, subcutaneous injection, intramuscular injection, pleural perfusion, intraperitoneal perfusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	In accordance with the internationally recognised CTCAE V6.0 toxicity assessment criteria	the study drug OVV-01 occurring within 3 weeks of the first dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs)	Incidence and severity of treatment-emergent adverse events (TEAEs) graded according to NCI CTCAE v5.0.	From signing ICF until 24 months after the last infusion
ORR	The proportion of subjects achieving CR or PR will be assessed according to RECIST 1.1.	Imaging assessments will be conducted within 28 days prior to first dose, every 6 weeks (±7 days) during treatment, and every 12 weeks during follow-up until disease progression，up to 24 months.
DCR	The proportion of subjects achieving CR, PR, or SD will be assessed according to RECIST 1.1.	Imaging assessments will be conducted within 28 days prior to first dose, every 6 weeks (±7 days) during treatment, and every 12 weeks during follow-up until disease progression，up to 24 months
PFS	The time from the first study treatment to the first documented disease progression or death from any cause (whichever occurs first) will be assessed according to RECIST 1.1.	Imaging assessments will be conducted within 28 days prior to first dose, every 6 weeks (±7 days) during treatment, and every 12 weeks during follow-up until disease progression，up to 24 months.
OS	The time from the first study treatment to death from any cause will be assessed according to RECIST 1.1.	Imaging assessments will be conducted within 28 days prior to first dose, every 6 weeks (±7 days) during treatment, and every 12 weeks during follow-up until disease progression，up to 24 months.

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Collaborators: Joint Biosciences Ltd.
• Investigators: Principal Investigator: Ning Li, The Cancer Hospital of the Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: September 30, 2026
• First Submitted That Met QC Criteria: September 30, 2026
• First Posted (Actual): October 5, 2026

Study Record Updates

• Last Update Posted (Actual): October 5, 2026
• Last Update Submitted That Met QC Criteria: September 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: CAR-Tumor-A01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No