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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04111510
Recruitment Status : Recruiting
First Posted : October 1, 2019
Last Update Posted : February 13, 2020
Sponsor:
Collaborator:
Iovance Biotherapeutics, Inc.
Information provided by (Responsible Party):
Michael Hurwitz, Yale University

Tracking Information
First Submitted Date  ICMJE September 30, 2019
First Posted Date  ICMJE October 1, 2019
Last Update Posted Date February 13, 2020
Actual Study Start Date  ICMJE December 23, 2019
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 30, 2019)
  • Objective response rate (ORR) [ Time Frame: Up to 3 years ]
    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.
  • Safety profile [ Time Frame: Up to 3 years ]
    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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2019)
  • Duration of response (DOR) [ Time Frame: Up to 3 years ]
    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.
  • Disease control rate (DCR) [ Time Frame: Up to 3 years ]
    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.
  • Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
    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.
  • Overall survival (OS) [ Time Frame: Up to 3 years ]
    To evaluate the efficacy of autologous LN-145 as a single therapy in Metastatic Triple Negative Breast patients overall survival (OS) will be used.
  • Complete response (CR) [ Time Frame: Up to 3 years ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Tumor Infiltrating Lymphocytes in Patients With Pretreated Metastatic Triple Negative Breast Cancer
Official Title  ICMJE A Phase 2 Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients With Pretreated Metastatic Triple Negative Breast Cancer
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Triple Negative Breast Cancer
Intervention  ICMJE Drug: Tumor infiltrating lymphocytes (TIL) LN-145

The TIL autologous therapy with LN-145 is comprised of the following steps:

  1. Tumor resection to provide the autologous tissue that serves as the source of the TIL cellular product;
  2. LN-145 investigational product production at a central Good Manufacturing Practice (GMP) facility;
  3. A 7-day nonmyeloablative lymphodepletion (NMA-LD) preconditioning regimen (hospitalization per institution standards);
  4. Infusion of the autologous LN-145 product on Day 0 (during inpatient hospitalization);
  5. Intravenous (IV) interleukin-2 (IL-2) administrations for up to six doses maximum (during inpatient hospitalization).
Study Arms  ICMJE Experimental: LN-145
LN-145 will be delivered as a single therapy in patients with Metastatic Triple Negative Breast Cancer.
Intervention: Drug: Tumor infiltrating lymphocytes (TIL) LN-145
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 30, 2019)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alexandra Dormal, RN 203-833-2701 alexandra.dormal@yale.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04111510
Other Study ID Numbers  ICMJE 2000025837
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Michael Hurwitz, Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Iovance Biotherapeutics, Inc.
Investigators  ICMJE
Principal Investigator: Michael Hurwitz, MD Yale University
PRS Account Yale University
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP