Clinical Trials /

Autologous Tumor Infiltrating Lymphocytes in Patients With Pretreated Metastatic Triple Negative Breast Cancer

NCT04111510

Description:

This study will investigate the safety and efficacy of TIL therapy in patients with metastatic TNBC who have progressed on at least one and no more than three prior systemic anticancer therapies.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Autologous Tumor Infiltrating Lymphocytes in Patients With Pretreated Metastatic Triple Negative Breast Cancer
  • Official Title: A Phase 2 Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients With Pretreated Metastatic Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2000025837
  • NCT ID: NCT04111510

Conditions

  • Metastatic Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
Tumor infiltrating lymphocytes (TIL) LN-145LN-145

Purpose

This study will investigate the safety and efficacy of TIL therapy in patients with metastatic TNBC who have progressed on at least one and no more than three prior systemic anticancer therapies.

Detailed Description

      The primary aims of the study are:

        -  To evaluate the efficacy of autologous LN-145 as a single therapy in Metastatic Triple
           Negative Breast Cancer (TNBC) patients by determining the objective response rate (ORR),
           using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, as assessed by the
           Investigator.

        -  To characterize the safety profile of tumor infiltrating lymphocytes (TIL) as a single
           therapy in Metastatic Triple Negative Breast Cancer patients as measured by the
           incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs).

      The secondary aims of the study are:

      • To further evaluate the efficacy of autologous LN-145 as a single therapy in Metastatic
      Triple Negative Breast Cancer patients using complete response duration of response (DOR),
      disease control rate (DCR), and progression-free survival (PFS), using RECIST 1.1, as
      assessed by the Investigator, overall survival (OS) and (CR) rate.
    

Trial Arms

NameTypeDescriptionInterventions
LN-145ExperimentalLN-145 will be delivered as a single therapy in patients with Metastatic Triple Negative Breast Cancer.
  • Tumor infiltrating lymphocytes (TIL) LN-145

Eligibility Criteria

        Inclusion Criteria:

          -  Ability to understand the requirements of the study. Specifically, the patient has to
             provide written informed consent (as evidenced by signature on an ICF approved by the
             Yale Human Investigation Committee (HIC).

          -  All patients must have a triple negative metastatic breast cancer (Estrogen Receptor
             negative, Progesterone Receptor negative, HER2 negative) as defined by the 2018 ASCO
             CAP guidelines.

          -  Patients must have a confirmed diagnosis of metastatic triple negative breast cancer
             (Stage IV) histologically confirmed as per American Joint Committee on Cancer [AJCC]
             staging system).

          -  Patients must have had at least one and no more than three prior lines of systemic
             anticancer therapies for metastatic disease.

          -  Patients must have at least one resectable lesion of a minimum 1.5 cm in diameter (or
             aggregate of 1.5 cm if multiple lesions are sampled) post-resection for TIL
             investigational product production.

          -  Patients must have remaining measurable disease as defined by RECIST 1.1 following
             tumor resection for TIL manufacturing

          -  Patients must be ≥ 18 years of age at the time of consent.

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0 or 1, and an estimated life expectancy of ≥ 3 months in the opinion of the
             Investigator.

          -  Female patients of childbearing potential or female partners of childbearing potential
             of male participants, must be willing to practice an approved method of birth control
             during treatment and for 12 months after receiving all protocol-related therapy.

          -  Patients must have adequate bone marrow function

          -  Patients must have adequate organ function:

          -  Patients must be seronegative for the human immunodeficiency virus (HIV1 and HIV2).

          -  Patients must have a washout period of 5 half-lives from last anticancer therapy prior
             to the first study treatment (ie, start of NMA-LD).

          -  Patients must have recovered from all prior anticancer treatment-related adverse
             events (TRAEs) to Grade ≤ 1 (per Common Terminology Criteria for Adverse Events
             [CTCAE], version 5.0).

          -  Patients must have provided written authorization for use and disclosure of protected
             health information.

          -  Must be able and willing to comply with the study visit schedule and protocol
             requirements including long-term follow-up (LTFU).

        Exclusion Criteria:

          -  Patients who have received an organ allograft or prior cell transfer therapy within
             the past 20 years that included a nonmyeloablative or myeloablative chemotherapy
             regimen.

          -  Patients with symptomatic and/or untreated brain metastases:

          -  Patients who are on systemic steroid therapy except for those requiring steroid for
             management of adrenal insufficiency.

          -  Patients who are pregnant or breastfeeding.

          -  Patients who have active medical illness(es) that would pose increased risk for study
             participation

          -  Patients who have received a live or attenuated vaccination within 28 days prior to
             the start of NMA-LD.

          -  Patients who have any form of primary immunodeficiency (such as severe combined
             immunodeficiency disease [SCID] and acquired immune deficiency syndrome [AIDS]).

          -  Patients with a history of hypersensitivity to any component of the study drugs.

          -  Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New
             York Heart Association (NYHA) Class II or higher.

          -  Patients who have obstructive or restrictive pulmonary disease and have a documented
             FEV1 (forced expiratory volume in 1 second) ≤ 60% of predicted normal.

          -  Patients who have had another primary malignancy within the previous 3 years (except
             for curatively treated localized malignancy that has not required treatment for
             greater than 1 year.

          -  Participation in another clinical study with an investigational product within 21 days
             of the initiation of NMA-LD treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 3 years
Safety Issue:
Description:To evaluate the efficacy of autologous LN-145 as a single therapy in Metastatic Triple Negative Breast Cancer (TNBC) patients by determining the objective response rate (ORR), using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, as assessed by the Investigator.

Secondary Outcome Measures

Measure:Duration of response (DOR)
Time Frame:Up to 3 years
Safety Issue:
Description:To evaluate the efficacy of autologous LN-145 as a single therapy in Metastatic Triple Negative Breast Cancer patients using complete response duration of response (DOR), using RECIST 1.1, as assessed by the Investigator will be used.
Measure:Disease control rate (DCR)
Time Frame:Up to 3 years
Safety Issue:
Description:To evaluate the efficacy of autologous LN-145 as a single therapy in Metastatic Triple Negative Breast Cancer patients using disease control rate (DCR), using RECIST 1.1, as assessed by the Investigator will be used.
Measure:Progression-free survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description:To evaluate the efficacy of autologous LN-145 as a single therapy in Metastatic Triple Negative Breast Cancer patients, progression-free survival (PFS), using RECIST 1.1, as assessed by the Investigator will be used.
Measure:Overall survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:To evaluate the efficacy of autologous LN-145 as a single therapy in Metastatic Triple Negative Breast patients overall survival (OS) will be used.
Measure:Complete response (CR)
Time Frame:Up to 3 years
Safety Issue:
Description:To evaluate the efficacy of autologous LN-145 as a single therapy in Metastatic Triple Negative Breast patients complete response, using RECIST 1.1, as assessed by the Investigator will be used.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yale University

Last Updated

February 11, 2020