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
Study ID
NCT05981001
Phase
PHASE1/PHASE2
Status
Recruiting
Apply to this trial

Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - 70 Years
Healthy Volunteers
Not accepted

Interventions

  • Surgery for harvesting tumor-draining lymph nodes — PROCEDURE
    A sample of the participant's tumor-draining lymph nodes will be collected and sent to the biotherapy center for LNL isolation and expansion.
  • Cyclophosphamide — DRUG
    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.
  • Fludarabine — DRUG
    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.
  • Tumor-draining lymph node-derived lymphocyte (LNL) — BIOLOGICAL
    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.
  • Interleukin-2 — BIOLOGICAL
    Eight to twelve hours after completing the LNL infusion, all participants will receive intermediate-dose decrescendo IL-2 IV.
  • Camrelizumab — BIOLOGICAL
    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.
  • Nab-paclitaxel — DRUG
    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.
  • Gemcitabine — DRUG
    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.
  • Carboplatin — DRUG
    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.

Study Details

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.

Key Dates

Start date
Aug 1, 2023
Status verified
Jul 2023
Primary completion
Apr 30, 2032
Completion
Apr 30, 2035

Study Design

Enrollment
170 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy
    Participants in both phase I and phase II portions receive LNL treatment, which consists of non-myeloablative lymphocyte depleting regimen of chemotherapy with cyclophosphamide and fludarabine, followed by infusion of LNL and interleukin-2. After LNL treatment, participants receive camrelizumab PLUS one of two background chemotherapy regimens at investigator's discretion: (1) nab-paclitaxel, OR (2) gemcitabine/carboplatin.
  • Active Comparator: Phase II: Camrelizumab + Chemotherapy
    The single-arm phase I study did not have this arm. Participants in phase II portion receive camrelizumab PLUS one of two background chemotherapy regimens at investigator's discretion: (1) nab-paclitaxel, OR (2) gemcitabine/carboplatin.

Primary Outcome Measure

Phase I: Incidence of Dose-Limiting Toxicity (DLT) [ Time Frame: From the LNL infusion up to 28 days post-infusion ]

Central Contacts

Related Studies