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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Nasopharynx Cancer
• Intervention / Treatment: Drug: U87 autologous CAR T-cell

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Haitao Wu, Ph.D; Phone Number: 13585504678; Email: eentwuhaitao@163.com
• Study Contact Backup: Name: Jian Chen, Ph.D; Phone Number: 18917785406; Email: wzcj21@163.com

Study Locations

• China
  • Shanghai, China, 200000
    • Recruiting
    • Eye ENT Hospital of Fudan University
    • Contact: Jian Chen, Ph.D; Phone Number: 18917785406; Email: chenjent@qq.com
    • Principal Investigator: Hongmeng Yu, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: U87 autologous CAR T-cell injection; Two stages: dose escalation and dose expansion	Drug: U87 autologous CAR T-cell; Treatment with U87 chimeric antigen receptor T-cell infusion.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of U87 CAR-T cells	Time at the maximal concentration(Tmax)	2 years post CAR T cell infusion
Pharmacokinetics of U87 CAR-T cells	Area under the concentration-time curve(AUC)	2 years post CAR T cell infusion
Pharmacokinetics of U87 CAR-T cells	The maximal concentration of eripheral blood (Cmax)	2 years post CAR T cell infusion
Pharmacodynamics of U87 CAR-T cells	Concentration levels of CAR-T-related serum cytokines such as IL-6, IFN γ, ferritin and CRP at each time point	2 years post CAR T cell infusion
Objective Response Rate (ORR), as assessed by Investigators	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.	2 years post CAR T cell infusion
Duration of response (DOR), as assessed by Investigators	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.	2 years post CAR T cell infusion
Overall survival (OS)	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.	2 years post CAR T cell infusion
Progression-free survival (PFS), as assessed by Investigators	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.	2 years post CAR T cell infusion
Disease control rate (DCR), as assessed by Investigators	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.	2 years post CAR T cell infusion

Collaborators and Investigators

• Sponsor: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): September 20, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: September 23, 2024
• First Submitted That Met QC Criteria: September 25, 2024
• First Posted (Actual): September 26, 2024

Study Record Updates

• Last Update Posted (Actual): September 26, 2024
• Last Update Submitted That Met QC Criteria: September 25, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Chimeric Antigen Receptor T Cell; U87
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Head and Neck Neoplasms; Nasopharyngeal Neoplasms
• Other Study ID Numbers: U87-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No