This is a phase I, open-label, non-randomized, multicenter, dose-escalation trial designed to evaluate the safety, tolerability, and preliminary anti-tumor activity of autologous p95HER2.CAR-TECH2Me T cells in patients with selected advanced HER2-positive (3+) cancers, including locally advanced, recurrent, or metastatic breast, gastric, endometrial, and other selected solid tumors. The study will also assess pharmacokinetics, pharmacodynamics, and immunogenicity of p95HER2.CAR-TECH2Me following intravenous administration.
Treatment consists of non-myeloablative lymphodepletion chemotherapy with cyclophosphamide and fludarabine administered on Days -4 to -2, followed by a single infusion of p95HER2.CAR-TECH2Me cells on Day 0. The investigational product is a live cell suspension of autologous CAR-T lymphocytes derived from the patient's peripheral blood. Premedication will be administered before cell infusion according to protocol requirements.
The primary objective of the study is to evaluate the safety and tolerability of p95HER2.CAR-TECH2Me and to identify the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). Primary endpoints include the nature and frequency of adverse events, serious adverse events, clinically relevant changes in laboratory parameters, electrocardiograms, vital signs, physical examination findings, and ECOG performance status, as well as the incidence and nature of dose-limiting toxicities. Adverse events will be graded according to NCI CTCAE v5.0, with cytokine release syndrome and neurotoxicity graded according to established consensus criteria.
Secondary objectives include evaluation of preliminary anti-tumor activity and survival outcomes. Secondary endpoints include objective response rate, duration of response, progression-free survival according to RECIST v1.1 as assessed by the investigator, and overall survival.
Approximately 15 patients are planned for enrollment over an estimated 36 to 48 months. The total study duration is expected to be approximately 60 months from the time the first subject signs the pre-screening informed consent form until the last subject completes the final study-related follow-up contact.
Patients must understand and voluntarily sign an informed consent document before any study-related assessments/procedures being conducted.
Age ≥ 18 and years at the time of signing the ICF
Patients must be able and willing to comply with the study visit schedule and protocol requirements.
Patients must have a clinical performance of Eastern Cooperative Oncology Group 0 or 1.
Patients with symptomatic and/or untreated brain metastases. Note: Patients with definitively-treated brain metastases will be considered for enrollment after discussion with Medical Monitor if prior to the start of NMA-LD the patient is asymptomatic, clinically stable for ≥3 months, there are no new brain lesions via magnetic resonance imaging (MRI) post-treatment, and the patient does not require corticosteroid treatment.
Patients with leptomeningeal carcinomatosis.
Patients with an active concurrent or history within the past 3 years of invasive malignancy, except for non-melanoma skin cancer, cervical and bladder carcinoma in situ, good prognosis ductal carcinoma in situ of the breast, or prostate carcinoma that is in remission under androgen deprivation therapy for > 2 years. Other exceptions may apply and require discussion between the Investigator and the Medical Monitor.
Patients with an active systemic infection requiring anti-infective treatment within 14 days before preparative lymphodepleting therapy.
Single group
p95HER2.CAR-TECH2Me
Biological/VaccineThe treatment includes NMA-LD chemotherapy (cyclophosphamide 500 mg/m²/day + fludarabine 30mg/m2/day for three days) and p95HER2.CAR-TECH2Me cell infusion (1 day). The p95HER2.CAR-TECH2Me product is a cellular investigational product comprising a live cell suspension of autologous CAR-T lymphocytes derived from the patient's peripheral blood.
Number of participants with adverse events and serious adverse events graded according to CTCAE v5.0
Adverse events and serious adverse events will be collected and summarized by frequency, severity, seriousness, and relationship to study treatment. Events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, when applicable. Cytokine release syndrome and neurotoxicity/ICANS will be graded according to the protocol-specified consensus grading criteria.
Number of participants with clinically significant abnormalities in clinical safety laboratory tests
Clinical safety laboratory assessments will be performed according to the Schedule of Assessments. Clinically significant new or worsening laboratory abnormalities will be recorded and summarized as adverse events when they meet protocol-defined adverse event criteria. Laboratory values will be assessed using local laboratory reference ranges. The protocol states that abnormal test findings are reported as AEs only if they are symptomatic, require additional testing/intervention or treatment, lead to study drug changes/discontinuation, or are considered AEs by the investigator or sponsor.
Number of participants with clinically significant abnormalities in 12-lead electrocardiogram findings
Twelve-lead electrocardiograms will be obtained according to the Schedule of Assessments. Clinically significant new or worsening ECG abnormalities will be summarized as adverse events when applicable.
Number of participants with clinically significant abnormalities in vital sign measurements
Vital signs will be assessed as part of the safety evaluations according to the protocol-specified time points. Clinically significant new or worsening abnormalities will be recorded and summarized as adverse events when applicable. The physical examination section specifies that vital signs, height and body weight are included in complete physical examinations.
Objective response rate according to RECIST v1.1 as assessed by the investigator
Objective response rate is defined as the percentage of participants with a confirmed complete response or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1, as assessed by the investigator.
Duration of response according to RECIST v1.1 as assessed by the investigator
Duration of response is defined as the time from the first documented objective response, complete response or partial response, to documented disease progression or death, whichever occurs first, in participants with confirmed complete response or partial response. Participants who are lost to follow-up or are alive and progression-free at the time of analysis will be censored at the last date they are known to be alive and progression-free.
Progression-free survival according to RECIST v1.1 as assessed by the investigator
Progression-free survival is defined as the time from start of study treatment to the date of confirmed disease progression, including radiographic or clinical progression, or death due to any cause, whichever occurs first.
Overall Survival (OS)
Overall survival is defined as the time from start of study treatment to death due to any cause. Participants who are alive at the time of analysis will be censored at the last date they are known to be alive or lost to follow-up.
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Vall d'Hebron Institute of Oncology
Lead sponsor
Banc de Sang i Teixits
Collaborator
Consorci Mar Parc de Salut de Barcelona
Collaborator
