A Phase I Interventional Open-label, Non-randomized Dose-escalation Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Preliminary Anti-tumor Activity of Autologous p95HER2.CAR-TECH2Me T Cells in Patients With Selected Advanced Cancers.

NCT07593820 | Recruiting Phase 1 DMC

• 2 other identifiers: VHIO240012024-516660-28-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Metastatic Gastric Cancer; Endometrial Cancer Metastatic; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (7)

• 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.

  Up to 3 months after the infusion

• 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.

  Up to 3 months after the infusion

• 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.

  Up to 3 months after the infusion

• 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.

  Up to 3 months after the infusion

• Number of participants with clinically significant abnormalities in physical examination findings

  Complete and targeted physical examinations will be performed according to the protocol. New or worsened clinically significant abnormalities identified after baseline will be recorded as adverse events and summarized by frequency.

  Up to 3 months after the infusion

• Change from baseline in Eastern Cooperative Oncology Group (ECOG)performance status score

  Performance status will be measured using the Eastern Cooperative Oncology Group Performance Status Scale. Scores range from 0 to 5, with higher scores indicating worse functional status.

  Up to 3 months after the infusion

• Number of participants with dose-limiting toxicities during the dose-limiting toxicity assessment period

  Dose-limiting toxicities will be assessed according to the protocol-defined DLT criteria and summarized by incidence and nature.

  28 days since the administration.

Secondary Outcomes (4)

• Objective response rate according to RECIST v1.1 as assessed by the investigator

  up to 2 years since the administration

• Duration of response according to RECIST v1.1 as assessed by the investigator

  up to 2 years since the administration

• Progression-free survival according to RECIST v1.1 as assessed by the investigator

  up to 2 years since the administration

• Overall Survival (OS)

  up to 2 years since the administration

Study Arms (1)

p95HER2.CAR-TECH2Me following lymphodepleting chemotherapy

EXPERIMENTAL

Participants will receive non-myeloablative lymphodepleting chemotherapy consisting of cyclophosphamide 500 mg/m²/day intravenously and fludarabine 30 mg/m²/day intravenously on Days -4 to -2, followed by a single intravenous infusion of autologous p95HER2.CAR-TECH2Me cells on Day 0. Premedication will be administered prior to p95HER2.CAR-TECH2Me infusion according to protocol requirements. The dose of p95HER2.CAR-TECH2Me will vary by dose-escalation cohort.

Biological: p95HER2.CAR-TECH2Me

Interventions

p95HER2.CAR-TECH2Me BIOLOGICAL

The 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.

p95HER2.CAR-TECH2Me following lymphodepleting chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Life expectancy ≥12 weeks.
• Patients must have histologically or cytologically proven unresectable or metastatic tumors. The disease must be refractory to standard therapy or in the first line if they are unable to receive standard therapy or no standard therapy exists for a particular disease.
• a) Select tumor types: breast, gastric, and endometrial tumors. Other selected solid tumors may be included per investigator discretion if the potential benefit is considered based on the literature updates in HER2/p95HER2 expression.
• Positivity for HER2 expression according to international society guidelines (score in a ISO-certified clinical or equivalent laboratory). To meet study entry eligibility, tumors are required to have at least an intensity score 3+ for HER2 staining following the manufacturer's recommendations
• Measurable disease by the RECIST v. 1.1 criteria (See Section 7.2 for details). Note: Lesions previously irradiated should not be selected as target lesions unless there has been demonstrated progression in those lesions;
• Patients are considered medically fit enough to undergo all study procedures and interventions and adequate hematological, renal, and hepatic functions defined by:
• Hemoglobin ≥ 9.0 g/dL.
• An absolute neutrophil count ≥ 1x10E9/L without the support of filgrastim
• Platelets ≥ 100 x10E9/L.
• PT and APTT ≤ 1.5x ULN (unless receiving therapeutic anticoagulation). Note: Subjects receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose.
• AST or ALT ≤ 3 x ULN. Patients with liver metastases must have AST and ALT ≤ 5.0 x ULN.

You may not qualify if:

• 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.
• Patients with active hepatitis B or hepatitis C.
• Patients with active autoimmune disease requiring immunosuppressive treatments.
• Patients with a history of organ or bone marrow transplantation.
• Patients with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
• Patients requiring regular treatment with steroids. Note: use of inhaled, topical steroids and use of systemic physiologic corticosteroid replacement therapy are permitted.
• Patients with current or history within the last 6 months, as determined by the Investigator, of clinically significant, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.
• Patients with a history of coronary revascularization or ischemic symptoms.
• History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin)
• Patients with allergies to any of the compounds included in any of the treatment products.
• Patients with contraindications for cyclophosphamide and fludarabine at per protocol doses (see Investigator Brochure for details).
• Patients who have received any approved anti-cancer cytotoxic, anti-angiogenic and ICB therapy including radiotherapy within 4 weeks before preparative lymphodepleting therapy.

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology: lead
• Banc de Sang i Teixits: collaborator
• Consorci Mar Parc de Salut de Barcelona: collaborator

Study Sites (2)

Hospital Del Mar

Barcelona, Catalonia, 08003, Spain

NOT YET RECRUITING

Hospital Universitari Vall D Hebron

Barcelona, Catalonia, 08035, Spain

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Breast Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Irene Braña, Dr

CONTACT

+932746085; ibrana@vhio.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2026
• First Posted: May 18, 2026
• Study Start: April 29, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): April 1, 2041
• Last Updated: May 22, 2026

Record last verified: 2025-12

Locations

ES (2)