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

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 phase I trial is mainly to study the safety of autologous LNL in patients with advanced HER2-negative breast cancer.

Conditions

• Breast Neoplasms

Interventions

PROCEDURE

Surgery 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.

DRUG

Cyclophosphamide

Cyclophosphamide will be administered at 500 mg/m\^2 IV daily for three days. Cyclophosphamide will be initiated five days prior to the anticipated LNL transfer, and the precise timing will depend on the rate of in vitro LNL growth.

DRUG

Fludarabine

Fludarabine will be administered at 30 mg/m\^2 IV daily for three days. Fludarabine will be initiated five days prior to the anticipated LNL transfer, and the precise timing will depend on the rate of in vitro LNL growth.

BIOLOGICAL

Tumor-draining lymph node-derived lymphocyte (LNL)

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

BIOLOGICAL

Interleukin-2

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

BIOLOGICAL

Camrelizumab

Camrelizumab will be administered at a dose of 200mg (3mg/kg for participants whose weight is below 50kg) IV on Day 1 of each 21-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared.

DRUG

Chemotherapeutic drug, ADC or PARP inhibitor

Another anti-tumor drug chosen from chemotherapeutic drug, ADC, or PARP inhibitor will be administered at investigator's discretion.

Sponsors & Collaborators

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

  lead OTHER

Principal Investigators

• Erwei Song, M.D., Ph.D. · Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-11-01

Primary Completion

2026-12-31

Completion

2031-12-31

Countries

• China

Study Locations