Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Analgesics

Antibodies

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunoglobulins

Interleukin-2

Poly(ADP-ribose) Polymerase Inhibitors

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Analgesics, Non-Narcotic

Enzyme Inhibitors

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.

A sample of the participant's tumor-draining lymph nodes will be collected and sent to the biotherapy center for LNL isolation and expansion.

Surgery for harvesting tumor-draining lymph nodes

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 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.

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).

Tumor-draining lymph node-derived lymphocyte (LNL)

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

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.

Camrelizumab

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

Chemotherapeutic drug, ADC or PARP inhibitor

Shicheng Su, M.D., Ph.D.

Erwei Song, M.D., Ph.D.

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.

Single-arm, dose-escalation and dose-expansion study

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

Adverse events are reported based upon Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. DLT will be defined as a non-hematologic Grade 3 or higher adverse event, occurring within the 28 days immediately after LNL infusion, that is probably or definitely related to LNL infusion, and lasts more than 28 days or does not resolve to Grade\<3 despite treatment with dexamethasone at 10 mg per 12 hours IV for 7 days (or other corticosteroid at equivalent dose), and/or tocilizumab at 8mg/kg IV for three times.

Adverse events are reported based upon CTCAE version 5.0 criteria. The incidence of Grade≥3 TEAE occurring within the 28 days immediately after LNL infusion will be summarized with descriptive statistics.

Objective response rate is defined as the percentage of participants in the analysis population who have achieved complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The percentage of participants who experienced a CR or PR is presented.

Disease control rate is defined as the percentage of participants who have achieved CR or PR or have demonstrated stable disease (SD) for at least 24 weeks, per RECIST 1.1.

For participants who demonstrate a confirmed CR or confirmed PR per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) per RECIST 1.1 or death due to any cause, whichever occurs first.

Progression-free survival is defined as the time from enrollment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurs first.

Overall survival is defined as the time from enrollment to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.

Levels of multiple different cytokines in blood samples including Granzyme B, IFN-γ, GM-CSF, IL-2, IL-4, IL-6, etc. will be measured using cytokine chips, ELISA or flow cytometry at various time points before and after LNL infusion.

Distribution of T cell subsets in blood samples will be measured using flow cytometry at various time points before and after LNL infusion.

Distribution of T-cell receptor (TCR) clonotype in blood samples will be measured using TCR sequencing at various time points before and after LNL infusion.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase I Study of Autologous Tumor-Draining Lymph Node-Derived Lymphocytes for Advanced HER2-Negative Breast Cancer	NCT06121557	Breast Neoplasm...	Surgery for har... Cyclophosphamid... Fludarabine Tumor-draining ... Interleukin-2 Camrelizumab Chemotherapeuti...	18 Years - 70 Years	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Phase I Study of Autologous Tumor-Draining Lymph Node-Derived Lymphocytes for Advanced HER2-Negative Breast Cancer	NCT06121557	Breast Neoplasm...	Surgery for har... Cyclophosphamid... Fludarabine Tumor-draining ... Interleukin-2 Camrelizumab Chemotherapeuti...	18 Years - 70 Years	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Spots Global Cancer Trial Database for chemotherapeutic drug, adc or parp inhibitor