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

Overview

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.

Interventions

• Drug U87 autologous CAR T-cell
  Treatment with U87 chimeric antigen receptor T-cell infusion.

Primary outcome measures

• Incidence of Adverse events after U87 CAR-T cells infusion [Safety and Tolerability] [Time frame: 28 days post administration of CAR-T-cells]

Secondary outcome measures (9)

• Pharmacokinetics of U87 CAR-T cells [Time frame: 2 years post CAR T cell infusion]
• Pharmacokinetics of U87 CAR-T cells [Time frame: 2 years post CAR T cell infusion]
• Pharmacokinetics of U87 CAR-T cells [Time frame: 2 years post CAR T cell infusion]
• Pharmacodynamics of U87 CAR-T cells [Time frame: 2 years post CAR T cell infusion]
• Objective Response Rate (ORR), as assessed by Investigators [Time frame: 2 years post CAR T cell infusion]
• Duration of response (DOR), as assessed by Investigators [Time frame: 2 years post CAR T cell infusion]
• Overall survival (OS) [Time frame: 2 years post CAR T cell infusion]
• Progression-free survival (PFS), as assessed by Investigators [Time frame: 2 years post CAR T cell infusion]
• Disease control rate (DCR), as assessed by Investigators [Time frame: 2 years post CAR T cell infusion]

Eligibility criteria

Inclusion criteria

• Subjects have provided informed consent, understanding the study\'s risks and benefits, and are willing to complete the study procedures.
• Age between 18 and 70 years old at the time of consent, inclusive, and open to both genders.
• ECOG performance status of 0-1.
• Anticipated survival of at least 12 weeks.
• Histologically or cytologically confirmed advanced malignant head and neck cancer patients with no effective standard treatments available
• Positive Trop2 expression (intensity ≥2+, expression rate ≥40%) in tumor tissue samples within 2 years prior to consent or from recent biopsies.
• At least one measurable tumor lesion according to RECIST 1.1.
• Suitable venous access for mononuclear cell collection.
• Adequate major organ function.
• 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

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

Pregnant or breastfeeding women.

• Uncontrollable psychiatric history.
• Other conditions deemed unsuitable for study participation by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Eye ENT Hospital of Fudan University — Shanghai

Identifiers

NCT: NCT06614686 · U87-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗