U87 CAR-T in Patients With Advanced Head and Neck Tumors

Phase 1

Recruiting

• Conditions: Nasopharynx Cancer; Head and Neck Cancer
• Interventions: Drug: U87 autologous CAR T-cell

• Registration Number: NCT06614686
• Lead Sponsor: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

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.

Study Timeline

• Status Verified: 2024-09
• Study Start: 2024-09-20
• Study First Submitted: 2024-09-23
• Study First Submitted QC: 2024-09-25
• Last Update Submitted: 2024-09-25
• Study First Posted: 2024-09-26
• Last Update Posted: 2024-09-26
• Primary Completion: 2026-10-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Subjects have provided informed consent, understanding the study'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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
U87 autologous CAR T-cell injection	U87 autologous CAR T-cell	Two stages: dose escalation and dose expansion

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse events after U87 CAR-T cells infusion [Safety and Tolerability]	28 days post administration of CAR-T-cells	An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of U87 CAR-T cells	2 years post CAR T cell infusion	The maximal concentration of eripheral blood (Cmax)
Pharmacodynamics of U87 CAR-T cells	2 years post CAR T cell infusion	Concentration levels of CAR-T-related serum cytokines such as IL-6, IFN γ, ferritin and CRP at each time point
Objective Response Rate (ORR), as assessed by Investigators	2 years post CAR T cell infusion	The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1.
Duration of response (DOR), as assessed by Investigators	2 years post CAR T cell infusion	Duration of response (DOR) is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death.
Overall survival (OS)	2 years post CAR T cell infusion	Overall Survival (OS) was defined as the time from the date of first infusion of U87 to the date of death due to any cause.
Progression-free survival (PFS), as assessed by Investigators	2 years post CAR T cell infusion	Progression-free survival (PFS) was defined as the time from the date of randomization to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause.
Disease control rate (DCR), as assessed by Investigators	2 years post CAR T cell infusion	Disease control rate (DCR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR) or Stable disease (SD) based on RECIST version 1.1.

Trial Locations

Locations (1)

Eye ENT Hospital of Fudan University; 🇨🇳 Shanghai, China