NCT05981001

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 170 (estimated)
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University · Academic / Other
• Sex: Female
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Breast Neoplasms

Interventions

Type	Name	Description
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 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.
DRUG	Fludarabine	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.
BIOLOGICAL	Tumor-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.
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 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.
DRUG	Nab-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.
DRUG	Gemcitabine	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.
DRUG	Carboplatin	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.

Timeline

• Start date: 2023-08-01
• Primary completion: 2032-04-30
• Completion: 2035-04-30
• First posted: 2023-08-08
• Last updated: 2023-08-08

Locations

1 site across 1 country: China