Clinical trial NCT06614686: U87 CAR-T in Patients With Advanced Head and Neck Tumors
Official title: A Single-arm, Open-label Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of U87 in Patients With Advanced Malignant Head and Neck Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Nasopharynx Cancer
Head and Neck Cancer
Keywords: Chimeric Antigen Receptor T Cell
U87
Lead sponsor: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
Sponsor class: INDUSTRY
First posted: 2024-09-26
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, open-label clinical study to evaluate the safety, tolerability, and efficacy of U87 injection solution in patients with advanced malignant head and neck tumors.

Detailed description: Following consent, patients must have tumor tissue evaluated by IHC assay. Patients meeting all eligibility criteria will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (U87). Following manufacture of the drug product, subjects will receive preconditioning prior to U87 infusion. All subjects will be asked to continue to undergo long-term gene safety follow-up.

Eligibility criteria: Inclusion Criteria:

1. Subjects have provided informed consent, understanding the study\&amp;#39;s risks and benefits, and are willing to complete the study procedures.
2. Age between 18 and 70 years old at the time of consent, inclusive, and open to both genders.
3. ECOG performance status of 0-1.
4. Anticipated survival of at least 12 weeks.
5. Histologically or cytologically confirmed advanced malignant head and neck cancer patients with no effective standard treatments available
6. Positive Trop2 expression (intensity ≥2+, expression rate ≥40%) in tumor tissue samples within 2 years prior to consent or from recent biopsies.
7. At least one measurable tumor lesion according to RECIST 1.1.
8. Suitable venous access for mononuclear cell collection.
9. Adequate major organ function.
10. Negative pregnancy test for women of reproductive age at screening; sexually active subjects must agree to use effective contraception during the study and for one year after the last CAR-T cell infusion.

Exclusion Criteria:

1. Inadequate washout period from prior anti-cancer treatments before leukapheresis.
2. Receipt of live or attenuated vaccines within 4 weeks prior to leukapheresis or planned receipt during the study.
3. Major surgery or significant trauma within 4 weeks prior to leukapheresis or planned during the study.
4. Previous Trop2-targeted CAR-T/TCR-T cell therapy or other cellular treatments, or therapeutic cancer vaccines.
5. Symptomatic brain metastases or leptomeningeal metastases deemed ineligible by the investigator.
6. Active infection requiring intravenous anti-infective therapy.
7. Positive for HBsAg, HBeAg, HBV-DNA, HCV-Ab, HCV-RNA, TP-Ab, HIV antibodies, or elevated EBV-DNA, CMV-DNA.
8. Primary immunodeficiency or active autoimmune disease.
9. Chronic use of systemic corticosteroids or immunosuppressants within 7 days before leukapheresis, except for local, ophthalmic, intra-articular, intranasal, or inhaled treatments.
10. Prior treatment-related adverse effects not recovered to CTCAE v5.0 grade ≤1 or specified levels, except for non-safety risk toxicities.
11. History of interstitial lung disease, interstitial pneumonia, pulmonary inflammation, or extensive thoracic radiotherapy.
12. Allergy to protein drugs or multiple medications.
13. Other untreated malignancies within 5 years prior to study drug use. History of immune deficiency, hematopoietic stem cell/organ transplantation. Uncontrollable third-space fluid accumulation.
14. Severe cardiovascular or cerebrovascular disease history, including NYHA class ≥II heart failure, uncontrolled hypertension, or recent severe events.

    Pregnant or breastfeeding women.
15. Uncontrollable psychiatric history.
16. Other conditions deemed unsuitable for study participation by the investigator.

Primary outcomes:
measure: Incidence of Adverse events after U87 CAR-T cells infusion [Safety and Tolerability]
timeFrame: 28 days post administration of CAR-T-cells
Secondary outcomes:
measure: Pharmacokinetics of U87 CAR-T cells
timeFrame: 2 years post CAR T cell infusion
measure: Pharmacokinetics of U87 CAR-T cells
timeFrame: 2 years post CAR T cell infusion
measure: Pharmacokinetics of U87 CAR-T cells
timeFrame: 2 years post CAR T cell infusion
measure: Pharmacodynamics of U87 CAR-T cells
timeFrame: 2 years post CAR T cell infusion
measure: Objective Response Rate (ORR), as assessed by Investigators
timeFrame: 2 years post CAR T cell infusion
measure: Duration of response (DOR), as assessed by Investigators
timeFrame: 2 years post CAR T cell infusion
measure: Overall survival (OS)
timeFrame: 2 years post CAR T cell infusion
measure: Progression-free survival (PFS), as assessed by Investigators
timeFrame: 2 years post CAR T cell infusion
measure: Disease control rate (DCR), as assessed by Investigators
timeFrame: 2 years post CAR T cell infusion
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Eye ENT Hospital of Fudan University
Study officials:
References: