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Advanced Breast CancerPhase 1/2NCT05812326

PD-1 Knockout Anti-MUC1 CAR-T Cells in the Treatment of Advanced Breast Cancer

A Phase 1/2 study testing AJMUC1- PD-1 gene knockout anti-MUC1 CAR-T cells in people with Advanced Breast Cancer and Breast Neoplasm Malignant Female, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This exploratory clinical study aims to assess the safety and preliminary efficacy of an immunotherapy using PD-1 knockout anti-MUC1 CAR-T cells in the treatment of advanced MUC1-positive breast cancer Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
AJMUC1- PD-1 gene knockout anti-MUC1 CAR-T cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteChina
Study dates
17 May 2019to 16 Nov 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient age: 18-70 years (including the boundary value);
  • Pathologically diagnosed with recurrent/metastatic breast cancer (except for intracranial metastasis), who have received at least one standard treatment regimen in the past, the disease is in a stable or progressive state, and refuses to undergo subsequent chemotherapy;
  • Abnormal glycosylated MUC1 expression confirmed by immunohistochemistry in tumor tissue or puncture tissue within 12 months;
  • Expected survival period ≥ 4 months;
  • ECOG score≤2 points;
  • The subjects voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with the follow-up;
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  • Able to cooperate with tumor puncture;
  • At least one measurable lesion that meets the RECIST v1.1 criteria;
  • Female patients of childbearing age must not be breastfeeding, and serum or urine HCG test is negative within 72 hours before study enrollment. All subjects must use medically approved contraception during the study period and within 3 months after the end of the study. measures (eg, IUDs, birth control pills) for contraception;
  • Organ function and bone marrow reserve are in good condition and the following requirements must be met: (1) The absolute value of neutrophils is ≥1.5×109/L; (2) Platelet count ≥75×109/L; (3) Hemoglobin ≥9g/dl; (4) Bilirubin value < 1.5 times the upper limit of normal (except for obstruction of the bile duct caused by tumor compression); (5) Creatinine value < 1.5 times the upper limit of normal or creatinine clearance rate ≥ 60ml/min; (6) ALT or AST < 2.5 times the upper limit of normal (with liver involvement < 5 times the upper limit of normal); (7) Stable coagulation function: INR≤1.5, PTT<1.2 times the upper limit of normal (except for tumor-related anticoagulation therapy).

Who cannot join

  • Have used immunosuppressive drugs or hormones within 1 week prior to enrollment;
  • Patients with moderate or more moderate pleural and ascites who need catheter drainage to relieve symptoms;
  • Human immunodeficiency virus (HIV) positive;
  • Active hepatitis B or C infection;
  • Pregnant or lactating women;
  • Past or concurrent history of other malignant tumors. Excluded: Patients with basal or squamous cell carcinoma of the skin and carcinoma in situ of the cervix who have been cured at any time prior to the study;
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  • Those with central transfer;
  • Serious, uncontrollable concomitant diseases that may affect protocol compliance or interfere with the interpretation of results, or have any serious medical conditions that may affect the subject's safety (such as uncontrollable heart disease, high blood pressure, active or uncontrollable disease) infection, etc.);
  • Active autoimmune diseases (including but not limited to, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.);
  • Those with a history of organ transplantation;
  • Subjects whose last medication was less than 2 weeks before enrollment, or subjects who participated in other relevant clinical studies at the same time;
  • Those who have received gene therapy in the past;
  • Vaccination with live vaccine within 4 weeks prior to study;
  • History of myocardial infarction and severe arrhythmia within half a year; uncontrolled hypertension, coronary heart disease, stroke, liver cirrhosis, nephritis and other serious complications;
  • Those who have a history of psychotropic substance abuse and cannot quit or who have a history of mental disorders;
  • Hypersensitivity constitution, allergic to human serum albumin;
  • Hemorrhagic and thrombotic tendency: patients with clinically significant bleeding symptoms or clear bleeding tendency within 3 months before the study, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, abnormal coagulation function (PT>16s, APTT>43s) , TT>21s, FIB<2g/L), hereditary or acquired bleeding and thrombosis tendency to (such as hemophilia, coagulation disorder, thrombocytopenia, hypersplenism, etc.), are receiving thrombolytic or anticoagulation therapy, arterial/venous thrombotic events occurred within the previous 6 months, such as cerebrovascular disease (including cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
  • Other severe, acute, or chronic medical or psychiatric conditions that may increase the risks associated with participation in the study or may interfere with the interpretation of the study results, in the opinion of the investigator.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Sun Yat-sen Memorial Hospital of Sun Yat-sen University

    Guangzhou, Guangdong, 510120

Other trials in China

About this study

Official title: Exploratory Clinical Study of PD-1 Knockout Targeting MUC1 CAR-T Cells (AJMUC1) in the Treatment of MUC1-positive Advanced Breast Cancer

This exploratory clinical study aims to assess the safety and preliminary efficacy of an immunotherapy using PD-1 knockout anti-MUC1 CAR-T cells in the treatment of advanced MUC1-positive breast cancer

Read the detailed description

This is a single-center, open-label, dose-escalation exploratory study investigating the safety,tolerability and preliminary efficacy of AJMUC1, PD-1 knockout CAR-T cells targeting aberrantly glycosylated MUC1, in the treatment of patients with advanced MUC1 positive breast cancer. The primary objective of this study is to evaluate the safety, tolerability, biological activity, and preliminary antitumor efficacy of AJMUC1. The study adopts a "3+3" dose escalation design to identify the maximum tolerated dose (MTD)/ maximum administered dose (MAD). Three doses are set: 3×105 CAR T cells/kg, 1×106 CAR T cells/kg and 3×106 CAR T cells/kg, with a total of 15 patients planned by the data cutoff date. Participants may receive one, two, three or more cycles of AJMUC1 infusion dependent on the adverse effects and potential clinical benefits.. This study is initiated by the investigators and approved by the Human Ethics Committee of Sun Yat-sen Memorial Hospital affiliated with Sun Yat-sen University. All patients have signed informed consent.

Being tested
AJMUC1- PD-1 gene knockout anti-MUC1 CAR-T cells
Keywords
Breast cancer, solid tumor, CAR-T cells, PD-1 knockout, MUC1
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AJMUC1- PD-1 gene knockout anti-MUC1 CAR-T cellsDrug

    Also called Therapeutic T cells

    AJMUC1 is a genetically modified T cell therapeutic product targeting the aberrantly glycosylated MUC1 protein. CAR targeting MUC1 is introduced into autologous T cells by lentiviral vector, so that T cells expressing the receptor can recognize and kill MUC1 positive tumor cells. Preclinical studies have shown that binding of scFv targeting MUC1 to the MUC1 epitope on the surface of the target cell can induce the costimulatory CD28 and CD3ζ costimulatory domains to activate downstream signaling pathways and promote T cell activation and expansion. Activated CAR-T cells secrete a series of inflammatory cytokines and chemokines, leading to apoptosis and necrosis of target tumor cells. Following introduction of a CAR structure, the PD-1 gene of CAR-T cells is knocked out using CRISPR/Cas9, so that the CAR-T cell does not express PD-1, resulting in improved tumor killing efficiency of AJMUC due to the release of inhibition in the signaling pathway PD-1/PD-L1 in the tumor microenvironment.

Study groups in NCT05812326
Study groupRoleWhat they receive
Treatment with AJMUC1--PD-1 knockout CAR-T cellsExperimentalAdvanced breast cancer patients with positive MUC1 expression are the indications of this clinical study. Current conventional treatments are ineffective for these patients or there is no effective treatment plan available for them. No control group is established and a single arm design is used. This clinical study is the first application of AJMUC1 in the clinical treatment of MUC1-positive advanced breast cancer patients. The main purpose is to assess the safety and feasibility of the product in clinical use. Therefore, according to the principle of "3+3" dose escalation design, this study explored the maximum tolerated dose of AJMUC1 for the treatment of MUC1-positive advanced breast cancer. At the same time, the efficacy of AJMUC1 in the treatment of MUC1-positive advanced breast cancer will be observed and factors that could affect the safety and efficacy of the therapy will be exploringly evaluated.
Receives: Drug: AJMUC1- PD-1 gene knockout anti-MUC1 CAR-T cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v5.0

    Measured: 3 years

  2. Incidence of treatment-emergent adverse events [safety and tolerability] of dose of PD-1 Knockout CAR-T cells will be assessed using CTCAE v5.0

    Measured: 3 years

  3. Monitoring the numbers of circulating AJMUC1 after infusion will be evaluated.

    Measured: up to 3 years

Secondary outcomes (4)

  1. Response rate will be assessed according to the revised RECIST guideline iRECIST

    Measured: 3 years

  2. Overall Survival - OS (Measure the time from enrollment to death)

    Measured: 3 years

  3. Progression free survival - PFS (Time from enrollment to date of first documented progression or date of death)

    Measured: 3 years

  4. Median CAR-T cell persistence--Will be measured by quantitative RT-PCR

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Apr 2023
  2. Study start17 May 2019
  3. Primary completion16 Nov 2022
  4. Study completion16 Nov 2022

Resources

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
Sequential
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05812326
Sponsor's protocol ID
2019-KY-001-003
Status last verified
Oct 2022
First submitted
11 Oct 2022
Last updated
13 Apr 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AJMUC1- PD-1 gene knockout anti-MUC1 CAR-T cells in people with Advanced Breast Cancer and Breast Neoplasm Malignant Female, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen 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 10 inclusion and 18 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: finished, as of the sponsor's last update on 13 Apr 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v5.0 (time frame: 3 years). 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?

On the ClinicalTrials.gov record for NCT05812326.

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 Apr 2023.

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