RecruitingPhase 1Phase 2NCT05981001

Study of Autologous Tumor-Draining Lymph Node-Derived Lymphocytes for Advanced HER2-Negative Breast Cancer

An Open-Label Phase I/II Study of Autologous Tumor-Draining Lymph Node-Derived Lymphocytes for Advanced HER2-Negative Breast Cancer

Sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Enrollment

170 participants

Start Date

Aug 1, 2023

Study Type

INTERVENTIONAL

Conditions

Breast Neoplasms

Summary

RATIONALE: Patients with HER2-negative advanced breast cancer have limited choice on targeted therapies, and often show only modest responses to available immunotherapies. Adoptive cell therapy with tumor-infiltrating lymphocytes has difficulties in preparing enough cells from solid tumors and overcoming the exhaustion and dysfunction of T cells, which limit its clinical use. Tumor-draining lymph node-derived lymphocytes (LNLs) that have abundant tumor-specific T cells, rather than exhausted T cells, are easier to produce. It is not yet known whether LNL treatment is safe and effective in patients with advanced HER2-negative breast cancer. PURPOSE: This open-label phase I/II trial is to study the safety and efficacy of autologous LNL in patients with advanced HER2-negative breast cancer.

Eligibility

Sex: FEMALEMin Age: 18 YearsMax Age: 70 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a new type of personalized immune cell therapy for women with advanced or metastatic HER2-negative breast cancer. Immune cells are collected from lymph nodes near the tumor, grown in a lab, and then given back to the patient to help fight the cancer. **You may be eligible if:** - You are a woman aged 18–70 - You have locally advanced, recurrent, or metastatic HER2-negative breast cancer - You have already tried at least one hormonal therapy or CDK4/6 inhibitor (for hormone receptor-positive cancer), or are a good candidate for chemotherapy - Your cancer has not been treated with the specific chemo or immunotherapy drugs planned in this study (or at least 12 months have passed since such treatment) **You may NOT be eligible if:** - You have serious ongoing infections, autoimmune disease, or organ problems - You are pregnant or breastfeeding - You have received prior treatment that disqualifies you from the immune cell collection procedure Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

PROCEDURESurgery for harvesting tumor-draining lymph nodes

A sample of the participant's tumor-draining lymph nodes will be collected and sent to the biotherapy center for LNL isolation and expansion.

DRUGCyclophosphamide

Cyclophosphamide will be administered at 60 mg/kg IV daily over approximately two hours for two days. Cyclophosphamide will be initiated seven days prior to the anticipated LNL transfer, and the precise timing will depend on the rate of in vitro LNL growth.

DRUGFludarabine

After administration of cyclophosphamide, fludarabine will then be infused at 25 mg/m\^2 intravenous piggyback (IVPB) daily over approximately 30 minutes for five days, starting five days prior to LNL transfer.

BIOLOGICALTumor-draining lymph node-derived lymphocyte (LNL)

In the dose-escalation portion of phase I study, participants receive ascending dose (1×10\^9\~18×10\^9), single Infusion of LNL on day 0. In the dose-expansion portion of phase I study, participants receive single infusion of LNL at the recommended phase 2 dose (RP2D). In the phase II study, participants receive single infusion of LNL at the RP2D.

BIOLOGICALInterleukin-2

Eight to twelve hours after completing the LNL infusion, all participants will receive intermediate-dose decrescendo IL-2 IV.

BIOLOGICALCamrelizumab

Camrelizumab will be administered at a fixed dose of 200mg IV on Day 1 of each 21-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared.

DRUGNab-paclitaxel

Nab-paclitaxel will be administered at 100 mg/m\^2 IV on Days 1, 8 and 15 of each 28-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared.

DRUGGemcitabine

Gemcitabine will be administered at 1000 mg/m\^2 IV on Days 1 and 8 of each 21-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared.

DRUGCarboplatin

Carboplatin will be administered at area under the concentration-time curve 2 (AUC 2) IV on Days 1 and 8 of each 21-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared.