Advanced Solid TumorsEarly Phase 1NCT06825455
Allogeneic B7H3 CAR-γδT Cell Therapy for Advanced Solid Tumors
A Early Phase 1 study testing Fludarabine, Cyclophosphamide and B7H3 CAR-γδT cells in people with Advanced Solid Tumors and Ovarian Cancers, run by Peking University at 1 site in China.
Trial summary
γδT cells can directly recognize non-peptide tumor antigens, such as IPP phosphorylated metabolites, without relying on specific major histocompatibility complexes (MHCs). This unique characteristic leads to a lower risk of graft-versus-host disease (GVHD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Ovarian Cancers, Peritoneal (metastatic) Cancer
- What is being tested?
- Fludarabine, Cyclophosphamide and B7H3 CAR-γδT cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2025to 31 Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years old, gender is not limited;
- Expected survival time ≥3 months;
- ECOG score 0~1;
- Patients who meet the clinical diagnostic criteria and have a clear pathological diagnosis of malignant solid tumors that have failed standard treatment;
- Tumor tissue samples (specimens within one year are recommended) positive for B7H3 by immunohistochemical (IHC) staining or flow assay;
- Presence of at least one evaluable lesion according to RECIST V1.1;
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- Tumors limited to peritoneal (metastatic) and ovarian cancer in patients in the laparotomy group;
- Substantially normal bone marrow reserve function and normal liver and renal function (laboratory tests need to be fulfilled before the first treatment with cell injection):
- Blood: white blood cell count (WBC) ≥3E9/L, lymphocyte count (LY) ≥0.8E9/L, hemoglobin (Hb) ≥80g/L, platelet (PLT) ≥75E9/L; Liver: ALT ≤ 3 × ULN; AST ≤ 3 × ULN; total bilirubin ≤ 3.0 × ULN; Kidney: serum creatinine ≤ 1.5 × upper limit of normal range (ULN); Heart: left ventricular ejection fraction ≥50% on echocardiography; lung: normal oxygen saturation without oxygen.
- Pregnancy test should be negative for women of childbearing potential and both men and women agree to use effective contraception during treatment and for 1 year thereafter;
- Be able to understand the requirements and matters of the trial and be willing to participate in the clinical study as required;
- Sign the trial informed consent form.
Who cannot join
- Known hypersensitivity, allergy, intolerance, or contraindication to cell infusion or any of the drug components that may be used in the study, including fludarabine and cyclophosphamide;
- Patients who have been continuously using immunosuppressive drugs within 1 month prior to cell infusion;
- Cerebrovascular accident or seizure within 6 months prior to signing the informed consent form;
- Symptomatic brain metastases;
- a known psychiatric or substance abuse disorder that would interfere with cooperation with the trial requirements;
- Hepatitis B surface antigen (HBsAg) positivity or hepatitis B core antibody (HBcAb) positivity and a peripheral blood test for hepatitis B virus (HBV) DNA titer that is not within the normal reference range; hepatitis C virus (HCV) antibody positivity and peripheral blood hepatitis C virus (HCV) RNA positivity; human immunodeficiency virus (HIV) antibody positivity; syphilis Positive for syphilis;
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- Serious cardiac disease: including, but not limited to, unstable angina pectoris, myocardial infarction (occurring within 6 months prior to screening), congestive heart failure (NYHA classification ≥ III), and severe arrhythmias;
- Presence of active or uncontrolled infections requiring systemic therapy (except for mild genitourinary and upper respiratory tract infections);
- has not recovered from acute toxic effects of prior therapy (prior therapy-induced hematologic or organ toxicity ≥ Grade 2, except for abnormalities related to study disease and medical history);
- have a confirmed diagnosis of an immunodeficiency
- suffering from an active infection requiring systemic therapy;
- a female subject of childbearing potential who plans to become pregnant within 2 years of cell infusion; or a male subject whose partner plans to become pregnant within 2 years of cell infusion;
- Participation in a clinical study of another innovative drug within 1 month prior to screening;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Beijing Cancer Hospital
Beijing
Changsong Qi, Ph.D, +86-13811394004, xiwangpku@126.com
About this study
Official title: Clinical Study of the Safety and Tolerability of B7H3 CAR-γδT Cell Injection in the Treatment of Advanced Solid Tumors
γδT cells can directly recognize non-peptide tumor antigens, such as IPP phosphorylated metabolites, without relying on specific major histocompatibility complexes (MHCs). This unique characteristic leads to a lower risk of graft-versus-host disease (GVHD). The clinical safety of γδT cells in allogeneic tumor therapies has been validated multiple times, highlighting their significant potential in developing universal CAR-T cell therapies.
B7H3 (CD276), a member of the B7 negative co-stimulatory molecule family, is minimally expressed or absent in normal tissues but highly expressed in various tumor tissues. As a result, B7H3 is regarded as a highly promising tumor-associated antigen and a universal drug target with substantial therapeutic potential.
By utilizing γδT cells as carrier cells, the development of universal B7H3 CAR-γδT cell injections for advanced solid tumors can effectively address risks such as autologous cell preparation failure and treatment delays. This innovative approach offers a highly efficient solution for solid tumor treatment and holds great promise for advancing immunotherapy in this field
Read the detailed description
This study is an open-label, dose-escalation exploratory clinical trial using γδ T cells derived from healthy donors, genetically engineered to express a chimeric antigen receptor (CAR) targeting B7H3 on their membrane. Preclinical in vitro and in vivo experiments demonstrated the modified CAR-γδ T cells possess specific cytotoxicity against B7H3-positive tumor cells.
According to the patients' disease conditions, they were divided into an intravenous infusion group and an intraperitoneal infusion group. Both groups underwent a dose-escalation study using the "3+3" design.
- Being tested
- Fludarabine, Cyclophosphamide, B7H3 CAR-γδT cells
- Keywords
- cell therapy, γδT, CAR-T
- Medical subject headings
- Ovarian Neoplasms, Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Intravenous infusion group:30mg/m2 x 3 days (Day-4~-2)
CyclophosphamideDrug
Intravenous infusion group:500mg/m2 x 3 days (Day-4~-2)
B7H3 CAR-γδT cellsBiological
A single infusion of 6.0×107 CAR+ cells, 2.0×108CAR+ cells, and 6.0×108CAR+ cells
| Study group | Role | What they receive |
|---|---|---|
| Intravenous infusion groups | Experimental | Patients with advanced solid tumor. A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, allogenic targeting B7H3 chimeric antigen receptor γδT cells. Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: B7H3 CAR-γδT cells |
| Abdominal infusion group | Experimental | Patients with ovarian cancer or peritoneal (metastatic) cancer.Before cell injection, for subjects with obvious ascites, the ascites should be pumped as clean as possible through peritoneal puncture, and then the abdomen should be rinsed with saline before the cell infusion is performed. Receives: Biological: B7H3 CAR-γδT cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events (AEs)
AE is defined as any adverse medical event from the date of randomization to 12 months after B7H3 CAR-γδT cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versushost disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.
Measured: 12 months
Secondary outcomes (7)
Best objective Response Rate
The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as the best response to treatment assessed by investigators and based on the RECIST 1.1 criterion.
Measured: 12 months
Duration of Response (DOR)
DOR is defined as the date of their first CR or PR (which is subsequently confirmed) to PD assessed by investigators and based on the RECIST 1.1 criterion, or death regardless of cause.
Measured: 12 months
Progression Free Survival (PFS)
PFS is defined as the time from the B7H3 CAR-γδT cells infusion date to the date of disease progression assessed by investigators and based on the RECIST 1.1 criterion, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
Measured: 12 months
Overall Survival (OS)
OS is defined as the time from B7H3 CAR-γδT cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
Measured: 12 months
Immunogenicity: Proportion of subjects with anti drug antibody (ADA)
ADAs include anti-donor γδT antibody or anti-B7H3 CAR single-chain variable fragment antibody.
Measured: 12 months
Pharmacodynamics
The cytokines mainly include interleukin-2 (IL-2 ), IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C reactive protein (CRP), ferritin. Peak was defined as the maximum post-baseline level of the cytokine.
Measured: Up to 28 days after infusion
Pharmacokinetics
Persistence of B7H3 CAR-γδT cell assessed by number in peripheral blood and ascites
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2025
- Study start1 Mar 2025 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shen Lin, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06825455
- Sponsor's protocol ID
- QH10407-ST-01（0）
- Status last verified
- Oct 2024
- First submitted
- 9 Feb 2025
- Last updated
- 13 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of the Safety and Tolerability of B7H3 CAR-γδT Cell Injection in the Treatment of Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT06825455
- Acronym / sponsor ID
- QH10407-ST-01（0）
- Keywords
- cell therapy, γδT, CAR-T
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Peking UniversityUniversity, hospital or other
- Study start
- 1 Mar 2025 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 13 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
γδT cells can directly recognize non-peptide tumor antigens, such as IPP phosphorylated metabolites, without relying on specific major histocompatibility complexes (MHCs). This unique characteristic leads to a lower risk of graft-versus-host disease (GVHD). The clinical safety of γδT cells in allogeneic tumor therapies has been validated multiple times, highlighting their significant potential in developing universal CAR-T cell therapies.
B7H3 (CD276), a member of the B7 negative co-stimulatory molecule family, is minimally expressed or absent in normal tissues but highly expressed in various tumor tissues. As a result, B7H3 is regarded as a highly promising tumor-associated antigen and a universal drug target with substantial therapeutic potential.
By utilizing γδT cells as carrier cells, the development of universal B7H3 CAR-γδT cell injections for advanced solid tumors can effectively address risks such as autologous cell preparation failure and treatment delays. This innovative approach offers a highly efficient solution for solid tumor treatment and holds great promise for advancing immunotherapy in this field
Detailed description
This study is an open-label, dose-escalation exploratory clinical trial using γδ T cells derived from healthy donors, genetically engineered to express a chimeric antigen receptor (CAR) targeting B7H3 on their membrane. Preclinical in vitro and in vivo experiments demonstrated the modified CAR-γδ T cells possess specific cytotoxicity against B7H3-positive tumor cells.
According to the patients' disease conditions, they were divided into an intravenous infusion group and an intraperitoneal infusion group. Both groups underwent a dose-escalation study using the "3+3" design.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous infusion groups | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Biological: B7H3 CAR-γδT cellsPatients with advanced solid tumor. A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, allogenic targeting B7H3 chimeric antigen receptor γδT cells. |
| Abdominal infusion group | Experimental | Biological: B7H3 CAR-γδT cellsPatients with ovarian cancer or peritoneal (metastatic) cancer.Before cell injection, for subjects with obvious ascites, the ascites should be pumped as clean as possible through peritoneal puncture, and then the abdomen should be rinsed with saline before the cell infusion is performed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥18 years old, gender is not limited;
- Expected survival time ≥3 months;
- ECOG score 0~1;
- Patients who meet the clinical diagnostic criteria and have a clear pathological diagnosis of malignant solid tumors that have failed standard treatment;
- Tumor tissue samples (specimens within one year are recommended) positive for B7H3 by immunohistochemical (IHC) staining or flow assay;
Key exclusion criteria (13 listed)
- Known hypersensitivity, allergy, intolerance, or contraindication to cell infusion or any of the drug components that may be used in the study, including fludarabine and cyclophosphamide;
- Patients who have been continuously using immunosuppressive drugs within 1 month prior to cell infusion;
- Cerebrovascular accident or seizure within 6 months prior to signing the informed consent form;
- Symptomatic brain metastases;
- a known psychiatric or substance abuse disorder that would interfere with cooperation with the trial requirements;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FludarabineIntravenous infusion group:30mg/m2 x 3 days (Day-4~-2) | Drug | Intravenous infusion groups |
| CyclophosphamideIntravenous infusion group:500mg/m2 x 3 days (Day-4~-2) | Drug | Intravenous infusion groups |
| B7H3 CAR-γδT cellsA single infusion of 6.0×107 CAR+ cells, 2.0×108CAR+ cells, and 6.0×108CAR+ cells | Biological | Abdominal infusion group, Intravenous infusion groups |
Primary outcome
Incidence of Adverse Events (AEs)
Time frame: 12 months
AE is defined as any adverse medical event from the date of randomization to 12 months after B7H3 CAR-γδT cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versushost disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.
7 secondary outcomes
Best objective Response Rate
Time frame: 12 months
Duration of Response (DOR)
Time frame: 12 months
Progression Free Survival (PFS)
Time frame: 12 months
Overall Survival (OS)
Time frame: 12 months
Immunogenicity: Proportion of subjects with anti drug antibody (ADA)
Time frame: 12 months
Pharmacodynamics
Time frame: Up to 28 days after infusion
Pharmacokinetics
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Fludarabine, Cyclophosphamide and B7H3 CAR-γδT cells in people with Advanced Solid Tumors and Ovarian Cancers, run by Peking University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lin Shen (010-88196561, doctorshenlin@sina.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events (AEs) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2025.