NCT05981014

Study of Autologous Tumor-Draining Lymph Node-Derived Lymphocytes as Neoadjuvant Therapy for HER2-Negative Breast Cancer

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 196 (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 breast cancer not responding to initial neoadjuvant chemotherapy might have lower chances for a pathologic complete response (pCR) at definitive surgery, indicating worse prognosis. Adoptive cell therapy has demonstrated efficacy in advanced breast cancer, but whether the addition of adoptive cell therapy to neoadjuvant chemotherapy could increase the pCR rate remains unclear. Tumor-draining lymph node-derived lymphocytes (LNLs) that have abundant tumor-reactive T cells, but not exhausted T cells, are easy to produce. It is not yet known whether LNL treatment is safe and effective in patients with HER2-negative breast cancer not responding to neoadjuvant chemotherapy. PURPOSE: This open-label phase I/II trial is to investigate the safety and efficacy of autologous LNL in patients with HER2-negative breast cancer not responding to neoadjuvant chemotherapy.

Conditions

• Breast Neoplasms

Interventions

Type	Name	Description
PROCEDURE	Sentinel Lymph Node Biopsy (SLNB)	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	Doxorubicin	Doxorubicin will be administered at 60 mg/m\^2 IV on Day 1 of Cycles 1-2 of the neoadjuvant chemotherapy of the study.
DRUG	Epirubicin	Epirubicin will be administered at 100 mg/m\^2 IV on Day 1 of Cycles 1-2 of the neoadjuvant chemotherapy of the study.
DRUG	Cyclophosphamide	Cyclophosphamide will be administered at 600 mg/m\^2 IV on Day 1 of Cycles 1-2 of the neoadjuvant chemotherapy of the study.
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.
DRUG	Nab-paclitaxel	Nab-paclitaxel will be administered at 260 mg/m\^2 IV on Day 1 of Cycles 3-6 of the neoadjuvant chemotherapy of the study.

Timeline

• Start date: 2023-08-01
• Primary completion: 2030-12-31
• Completion: 2035-05-31
• First posted: 2023-08-08
• Last updated: 2023-08-08

Locations

1 site across 1 country: China