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

Plain English Summary

PD-1 Knockout Anti-MUC1 CAR-T Cells in the Treatment of Advanced Breast Cancer is a Phase 2 clinical trial sponsored by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University studying Advanced Breast Cancer, Breast Neoplasm Malignant Female. This study tested a new type of immunotherapy called AJMUC1, which uses modified T-cells to fight cancer. It was for women with advanced breast cancer that has returned or spread, and whose tumors have a specific marker called MUC1. Participants received the AJMUC1 treatment and were monitored for side effects and how well it worked. Standard treatments like chemotherapy were an alternative for patients who did not join this trial. The trial aims to enroll 15 participants.

Official 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

Who Can Participate

Here is what you need to know about eligibility for this trial. Women aged 18-70 with advanced breast cancer that has spread and has MUC1 markers. Patients must have had at least one prior treatment and are not candidates for or refuse further chemotherapy. Individuals must have a good general health status, with adequate organ and bone marrow function. People with certain other cancers, active infections, autoimmune diseases, or a history of organ transplant cannot join. This trial is studying Advanced Breast Cancer, Breast Neoplasm Malignant Female, so participants generally need a confirmed diagnosis.

What They're Measuring

The study measured how safe the treatment was by tracking side effects and how well the modified T-cells persisted in the body. The specific primary outcome measures are: Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v5.0 (3 years); 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 (3 years); Monitoring the numbers of circulating AJMUC1 after infusion will be evaluated. (up to 3 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial explores a novel CAR-T cell therapy for advanced breast cancer, addressing a need for new treatments when standard options are exhausted. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Advanced Breast Cancer, Breast Neoplasm Malignant Female, where improved treatment options are needed.

Investor Insight

This early-phase trial investigates a targeted immunotherapy for a specific breast cancer subtype, representing a growing area of cancer treatment with potential for future market entry. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if your cancer has the MUC1 marker and if this type of immunotherapy is suitable for you. Participation involves receiving the AJMUC1 infusion and regular check-ups to monitor your health and response to treatment. You will need to provide blood samples for testing and potentially undergo tumor biopsies. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 15 participants

Interventions

• DRUG: AJMUC1- PD-1 gene knockout anti-MUC1 CAR-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

Primary Outcomes

• Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v5.0 (3 years)
• 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 (3 years)
• Monitoring the numbers of circulating AJMUC1 after infusion will be evaluated. (up to 3 years)

Secondary Outcomes

• Response rate will be assessed according to the revised RECIST guideline iRECIST (3 years)
• Overall Survival - OS (Measure the time from enrollment to death) (3 years)
• Progression free survival - PFS (Time from enrollment to date of first documented progression or date of death) (3 years)
• Median CAR-T cell persistence--Will be measured by quantitative RT-PCR (3 years)

Full Eligibility Criteria

Inclusion Criteria:

1. Patient age: 18-70 years (including the boundary value);
2. 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;
3. Abnormal glycosylated MUC1 expression confirmed by immunohistochemistry in tumor tissue or puncture tissue within 12 months;
4. Expected survival period ≥ 4 months;
5. ECOG score≤2 points;
6. The subjects voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with the follow-up;
7. Able to cooperate with tumor puncture;
8. At least one measurable lesion that meets the RECIST v1.1 criteria;
9. 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;
10. 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).

Exclusion Criteria:

1. Have used immunosuppressive drugs or hormones within 1 week prior to enrollment;
2. Patients with moderate or more moderate pleural and ascites who need catheter drainage to relieve symptoms;
3. Human immunodeficiency virus (HIV) positive;
4. Active hepatitis B or C infection;
5. Pregnant or lactating women;
6. 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;
7. Those with central transfer;
8. 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.);
9. Active autoimmune diseases (including but not limited to, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.);
10. Those with a history of organ transplantation;
11. Subjects whose last medication was less than 2 weeks before enrollment, or subjects who participated in other relevant clinical studies at the same time;
12. Those who have received gene therapy in the past;
13. Vaccination with live vaccine within 4 weeks prior to study;
14. History of myocardial infarction and severe arrhythmia within half a year; uncontrolled hypertension, coronary heart disease, stroke, liver cirrhosis, nephritis and other serious complications;
15. Those who have a history of psychotropic substance abuse and cannot quit or who have a history of mental disorders;
16. Hypersensitivity constitution, allergic to human serum albumin;
17. 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;
18. 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

• Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Metastatic Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• HER2-Positive Breast Cancer
• Triple-Negative Breast Cancer
• Immunotherapy
• CAR-T Cell Therapy
• Targeted Therapy
• Oncology
• Malignant Neoplasms

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