HER2 Positive Advanced Solid TumorsPhase 1/2NCT05681650
HER2 Targeted HypoSti.CAR-T Cells in HER2 Positive Advanced Solid Tumors
A Phase 1/2 study testing HypoSti.CAR-HER2 T cells, Albumin-bound paclitaxel and Cyclophosphamide in people with HER2 Positive Advanced Solid Tumors, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
Chimeric antigen receptor modified T (CAR-T) cell therapy still has multiple difficulties in solid tumors, such as absence of tumor specific antigens, complex immunosuppressive tumor microenvironment, and tumor heterogeneity. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- HER2 Positive Advanced Solid Tumors
- What is being tested?
- HypoSti.CAR-HER2 T cells, Albumin-bound paclitaxel and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 11 Oct 2023to 31 Dec 2026
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Age from 18 to 75 years with estimated life expectancy >3 months.
- 2. Histopathological confirmed advanced or metastatic solid tumors failed to at least first-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy. HER2 antigen expression percentage ≥ 30%.
- 3. Have at least one measurable target lesion.
- 4. Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 6 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor rebiopsy in the process of this study.
- 5. Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to <= grade 1 toxicity.
- 6. Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 2 at the time of enrollment.
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- 7. Have adequate organ function, which should be confirmed within 2 weeks prior to the first dose of study drugs.
- 8. Previous treatment with anti-PD-1/PD-L1 antibodies are allowed.
- 9. Ability to understand and sign a written informed consent document.
- 10. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and up to 90 days after the last dose of the drug.
Who cannot join
- 1. Active, known or suspected autoimmune diseases.
- 2. Known brain metastases or active central nervous system (CNS). Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.
- 3. Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
- 4. History of severe hypersensitive reactions to other monoclonal antibodies.
- 5. History of allergy or intolerance to study drug components.
- 6. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
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- 7. History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.
- 8. Uncontrolled intercurrent illness, including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
- 9. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
- 10. Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.
- 11. Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
- 12. Vaccination within 30 days of study enrollment.
- 13. Active bleeding or known hemorrhagic tendency.
- 14. Subjects with unhealed surgical wounds for more than 30 days.
- 15. Being participating any other trials or withdraw within 4 weeks.
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, 1 recruiting
- Recruiting
Kaichao Feng
Beijing, Beijing Municipality, +86100853
Kaichao Feng, MD, +861066947300, timothyfkc@126.com
About this study
Official title: Phase I/II Clinical Trial of HER2 Targeted HypoSti.CAR-T Cells in Treating Patients With HER2 Positive Local Advanced or Metastatic Solid Tumors
Chimeric antigen receptor modified T (CAR-T) cell therapy still has multiple difficulties in solid tumors, such as absence of tumor specific antigens, complex immunosuppressive tumor microenvironment, and tumor heterogeneity. In this study, investigators developed a novel hypoxia-stimulated CAR expression system (HypoSti.CAR) that could enable CAR-T cell effectively expand and survive in hypoxic tumor microenvironment. After accomplishment of animal model verification, investigators conduct this clinical trial in order to assess the in vivo safety, feasibility and efficacy of HypoSti.CAR-HER2 T cells in HER2 antigen positive advanced solid tumors.
Read the detailed description
Currently, chimeric antigen receptor modified T (CAR-T) cell therapy has achieved a series of achievements in hematological malignancies, however, it still has to face plenty of obstacles in more bulky solid tumors, such as absence of tumor specific antigens, complex immunosuppressive tumor microenvironment, and tumor heterogeneity, which may taken together to restrict the efficacy of CAR-T cells in eliminating solid tumors. Previous studies found that intratumoral hypoxic microenvironment facilitated the development and metastasis of tumor cells. Meanwhile, it was difficult for cytotoxic T cells including CAR-T cells to survive and expand in such a hypoxic microenvironment.
In this study, investigators developed a novel hypoxia-stimulated CAR expression system (HypoSti.CAR) that could enable CAR-T cell effectively expand and survive in hypoxic tumor microenvironment,which has been demonstrated in animal models. Based on the preclinical data, investigators will further conduct this clinical trial in order to test the potential of this novel system targeting HER2 antigen in vivo. In dose escalation period, at least 9 eligible patients will be enrolled and receive 5 doses of HypoSti.CAR-HER2 T cell therapy (1 × 10^6 cells/kg, 3 × 10^6 cells/kg, 6 × 10^6 cells/kg,1 × 10^7 cells/kg, 1.5 × 10^7 cells/kg) according to the "3+3" principle. In dose expansion period, additional 10 to 21 patients will be enrolled to receive HypoSti.CAR-HER2 T cell therapy at dose of recommended phase 2 dose (RP2D), which is determined by data from dose escalation period, including occurrence of dose limiting toxicities (DLT), pharmacokinetics/pharmacodynamics, efficacy and other parameters, to furtherly evaluate the safety and efficacy profiles of HypoSti.CAR-HER2 T cell therapy.
- Conditions
- HER2 Positive Advanced Solid Tumors
- Being tested
- HypoSti.CAR-HER2 T cells, Albumin-bound paclitaxel, Cyclophosphamide, Fludarabine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HypoSti.CAR-HER2 T cellsBiological
Dose escalation: dose -1 (1×10^6 cells/kg) ,dose 1 (3×10^6 cells/kg) , dose 2 (6×10^6 cells/kg), dose 3 (1×10^7 cells/kg), dose 4 (1.5×10^7 cells/kg). Dose expansion: RP2D
Albumin-bound paclitaxelDrug
Administered intravenously at dose of 100-200mg/m2 on day -5
CyclophosphamideDrug
Administered intravenously at a total dose of 15-30mg/kg on day -3 and day-2
FludarabineDrug
Administered intravenously at dose of 30mg/m2/d on day -3 and day -2 only in the first infusion of HypoSti.CAR-HER2 T cells
| Study group | Role | What they receive |
|---|---|---|
| HypoSti.CAR-HER2 T cells | Experimental | Enrolled participants will be given a preconditioning regimen consisted of albumin-bound paclitaxel, cyclophosphamide and/or fludarabine before the infusion of HypoSti.CAR-HER2 T cells. Fludarabine will be administered only before the first dose infusion, and will not be administered before the secondary or multiple doses of HypoSti.CAR-HER2 T cell infusion. Receives: Biological: HypoSti.CAR-HER2 T cells; Drug: Albumin-bound paclitaxel; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment related adverse events
Treatment related adverse events are defined as any medical events since the initiation of preconditioning chemotherapy. Adverse events will be graded by CTCAE V5.0
Measured: Up to 12 months following the infusion of HypoSti.CAR-HER2 T cells
Incidence of dose limiting toxicities (DLTs)
Dose limiting toxicities are defined as HypoSti.CAR-HER2 T cell related adverse events within the first 28 days that meet the following criteria: grade 3 or higher CRS or CRES, grade 3 or higher cutaneous/ mucosal toxicity, and any other grade 4 toxicities.
Measured: Up to 28 days following the infusion of HypoSti.CAR-HER2 T cells
Determination of the maximum tolerated dose (MTD)
Maximum tolerated dose is defined as the highest dose that is less than or equal to 2 DLT among 6 subjects.
Measured: Up to 28 days following the infusion of HypoSti.CAR-HER2 T cells
Secondary outcomes (6)
Objective response rate (ORR)
Objective response rate is defined as complete response (CR) or partial response (PR) by RECIST 1.1or iRECIST
Measured: Up to 3 years
Time to response (TTR)
Time to response is defined as the time from HypoSti.CAR-HER2 T cell infusion to first assessed CR or PR by investigators according to RECIST 1.1or iRECIST.
Measured: Up to 3 years
Duration of response (DOR)
Duration of response is defined as the time from objective response (OR) until documented tumor progression date among responders.
Measured: Up to 3 years
Progression Free Survival (PFS)
Progression Free Survival is defined as the time from HypoSti.CAR-HER2 T cell infusion to documented disease progression or death.
Measured: Up to 3 years
Overall Survival (OS)
Overall Survival is defined as the time from HypoSti.CAR-HER2 T cell infusion to the date of death.
Measured: Up to 3 years
Number and copy number of HypoSti.CAR-HER2 T cell
Number and copy number of HypoSti.CAR-HER2 T cell are assessed by number in peripheral blood and tumor tissue.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2023
- Study start11 Oct 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2 Positive Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- 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
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fudan University
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
- Investigators
- Jianqing Xu, PhD, Study director, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05681650
- Sponsor's protocol ID
- CHN-PLAGH-BT-076
- Status last verified
- Dec 2023
- First submitted
- 27 Dec 2022
- Last updated
- 12 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Clinical Trial of HER2 Targeted HypoSti.CAR-T Cells in Treating Patients With HER2 Positive Local Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT05681650
- Acronym / sponsor ID
- CHN-PLAGH-BT-076
- Conditions
- HER2 Positive Advanced Solid Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Collaborators
- Fudan University
- Study start
- 11 Oct 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 12 Jan 2023 (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.
Chimeric antigen receptor modified T (CAR-T) cell therapy still has multiple difficulties in solid tumors, such as absence of tumor specific antigens, complex immunosuppressive tumor microenvironment, and tumor heterogeneity. In this study, investigators developed a novel hypoxia-stimulated CAR expression system (HypoSti.CAR) that could enable CAR-T cell effectively expand and survive in hypoxic tumor microenvironment. After accomplishment of animal model verification, investigators conduct this clinical trial in order to assess the in vivo safety, feasibility and efficacy of HypoSti.CAR-HER2 T cells in HER2 antigen positive advanced solid tumors.
Detailed description
Currently, chimeric antigen receptor modified T (CAR-T) cell therapy has achieved a series of achievements in hematological malignancies, however, it still has to face plenty of obstacles in more bulky solid tumors, such as absence of tumor specific antigens, complex immunosuppressive tumor microenvironment, and tumor heterogeneity, which may taken together to restrict the efficacy of CAR-T cells in eliminating solid tumors. Previous studies found that intratumoral hypoxic microenvironment facilitated the development and metastasis of tumor cells. Meanwhile, it was difficult for cytotoxic T cells including CAR-T cells to survive and expand in such a hypoxic microenvironment.
In this study, investigators developed a novel hypoxia-stimulated CAR expression system (HypoSti.CAR) that could enable CAR-T cell effectively expand and survive in hypoxic tumor microenvironment,which has been demonstrated in animal models. Based on the preclinical data, investigators will further conduct this clinical trial in order to test the potential of this novel system targeting HER2 antigen in vivo. In dose escalation period, at least 9 eligible patients will be enrolled and receive 5 doses of HypoSti.CAR-HER2 T cell therapy (1 × 10^6 cells/kg, 3 × 10^6 cells/kg, 6 × 10^6 cells/kg,1 × 10^7 cells/kg, 1.5 × 10^7 cells/kg) according to the "3+3" principle. In dose expansion period, additional 10 to 21 patients will be enrolled to receive HypoSti.CAR-HER2 T cell therapy at dose of recommended phase 2 dose (RP2D), which is determined by data from dose escalation period, including occurrence of dose limiting toxicities (DLT), pharmacokinetics/pharmacodynamics, efficacy and other parameters, to furtherly evaluate the safety and efficacy profiles of HypoSti.CAR-HER2 T cell therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HypoSti.CAR-HER2 T cells | Experimental | Biological: HypoSti.CAR-HER2 T cells, Drug: Albumin-bound paclitaxel, Drug: Cyclophosphamide, Drug: FludarabineEnrolled participants will be given a preconditioning regimen consisted of albumin-bound paclitaxel, cyclophosphamide and/or fludarabine before the infusion of HypoSti.CAR-HER2 T cells. Fludarabine will be administered only before the first dose infusion, and will not be administered before the secondary or multiple doses of HypoSti.CAR-HER2 T cell infusion. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 1. Age from 18 to 75 years with estimated life expectancy >3 months.
- 2. Histopathological confirmed advanced or metastatic solid tumors failed to at least first-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy. HER2 antigen expression percentage ≥ 30%.
- 3. Have at least one measurable target lesion.
- 4. Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 6 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor rebiopsy in the process of this study.
- 5. Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to <= grade 1 toxicity.
Key exclusion criteria (15 listed)
- 1. Active, known or suspected autoimmune diseases.
- 2. Known brain metastases or active central nervous system (CNS). Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.
- 3. Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
- 4. History of severe hypersensitive reactions to other monoclonal antibodies.
- 5. History of allergy or intolerance to study drug components.
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 |
|---|---|---|
| HypoSti.CAR-HER2 T cellsDose escalation: dose -1 (1×10^6 cells/kg) ,dose 1 (3×10^6 cells/kg) , dose 2 (6×10^6 cells/kg), dose 3 (1×10^7 cells/kg), dose 4 (1.5×10^7 cells/kg). Dose expansion: RP2D | Biological | HypoSti.CAR-HER2 T cells |
| Albumin-bound paclitaxelAdministered intravenously at dose of 100-200mg/m2 on day -5 | Drug | HypoSti.CAR-HER2 T cells |
| CyclophosphamideAdministered intravenously at a total dose of 15-30mg/kg on day -3 and day-2 | Drug | HypoSti.CAR-HER2 T cells |
| FludarabineAdministered intravenously at dose of 30mg/m2/d on day -3 and day -2 only in the first infusion of HypoSti.CAR-HER2 T cells | Drug | HypoSti.CAR-HER2 T cells |
Primary outcome
Incidence of treatment related adverse events
Time frame: Up to 12 months following the infusion of HypoSti.CAR-HER2 T cells
Treatment related adverse events are defined as any medical events since the initiation of preconditioning chemotherapy. Adverse events will be graded by CTCAE V5.0
Incidence of dose limiting toxicities (DLTs)
Time frame: Up to 28 days following the infusion of HypoSti.CAR-HER2 T cells
Dose limiting toxicities are defined as HypoSti.CAR-HER2 T cell related adverse events within the first 28 days that meet the following criteria: grade 3 or higher CRS or CRES, grade 3 or higher cutaneous/ mucosal toxicity, and any other grade 4 toxicities.
Determination of the maximum tolerated dose (MTD)
Time frame: Up to 28 days following the infusion of HypoSti.CAR-HER2 T cells
Maximum tolerated dose is defined as the highest dose that is less than or equal to 2 DLT among 6 subjects.
6 secondary outcomes
Objective response rate (ORR)
Time frame: Up to 3 years
Time to response (TTR)
Time frame: Up to 3 years
Duration of response (DOR)
Time frame: Up to 3 years
Progression Free Survival (PFS)
Time frame: Up to 3 years
Overall Survival (OS)
Time frame: Up to 3 years
Number and copy number of HypoSti.CAR-HER2 T cell
Time frame: Up to 3 years
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 12 Dec 2023.
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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.
Jianqing Xu, PhD study director
Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HypoSti.CAR-HER2 T cells, Albumin-bound paclitaxel and Cyclophosphamide in people with HER2 Positive Advanced Solid Tumors, run by Chinese PLA General Hospital 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 10 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 12 Dec 2023. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Kaichao Feng, MD (+861066947300, timothyfkc@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment related adverse events (time frame: Up to 12 months following the infusion of HypoSti.CAR-HER2 T cells). The study lists 3 primary outcomes in all. 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 12 Dec 2023.