Phase I 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
NCT06121557
Phase
PHASE1
Status
Recruiting
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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 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.
  • Fludarabine — DRUG
    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.
  • Tumor-draining lymph node-derived lymphocyte (LNL) — BIOLOGICAL
    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).
  • 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 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.
  • Chemotherapeutic drug, ADC or PARP inhibitor — DRUG
    Another anti-tumor drug chosen from chemotherapeutic drug, ADC, or PARP inhibitor will be administered at investigator's discretion.

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

Key Dates

Start date
Nov 1, 2023
Status verified
Nov 2023
Primary completion
Dec 31, 2026
Completion
Dec 31, 2031

Study Design

Enrollment
24 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: LNL treatment + Camrelizumab + another anti-tumor drug
    Participants 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 another anti-tumor drug chosen from chemotherapeutic drug, ADC, or PARP inhibitor at investigator's discretion.

Primary Outcome Measure

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

Central Contacts

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