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

NCT04111510 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2000025837
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  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. Upon results entry, the time frame was updated to reflect the latest time point that a participant was assessed for ORR in the study.

  Up to 4 months

• Safety Profile

  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). Incidence is presented as a count of participants that experienced at least 1 TEAE of Grade ≥ 3.

  Up to 3 years

Secondary Outcomes (5)

• Duration of Response (DOR) in Days

  Up to 3 years

• Disease Control Rate (DCR)

  Up to 3 years

• Progression-free Survival (PFS)

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

• Complete Response (CR)

  Up to 3 years

Study Arms (1)

LN-145

EXPERIMENTAL

LN-145 will be delivered as a single therapy in patients with Metastatic Triple Negative Breast Cancer.

Drug: Tumor infiltrating lymphocytes (TIL) LN-145

Interventions

Tumor infiltrating lymphocytes (TIL) LN-145 DRUG

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).

LN-145

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 disease progression from the last line of therapy.
• 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 the following hematologic parameters:
• Absolute neutrophil count (ANC) ≥ 1000/mm3;
• Hemoglobin ≥ 9.0 g/dL;
• Platelet count ≥ 100,000/mm3
• Patients must have adequate organ function.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• Iovance Biotherapeutics, Inc.: collaborator

Study Sites (1)

Yale School of Medicine

New Haven, Connecticut, 06520, United States

Location

Related Publications (1)

• Gautam N, Elleson KM, Ramamoorthi G, Czerniecki BJ. Current State of Cell Therapies for Breast Cancer. Cancer J. 2022 Jul-Aug 01;28(4):301-309. doi: 10.1097/PPO.0000000000000607.

  PMID: 35880940 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Toll-Like Receptor 1

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Toll-Like Receptors; Receptors, Pattern Recognition; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Michael Hurwitz, MD, PhD
• Organization: Yale School of Medicine

michael.hurwitz@yale.edu

(877) 925-3637

Study Officials

• Michael Hurwitz, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2019
• First Posted: October 1, 2019
• Study Start: December 23, 2019
• Primary Completion: January 30, 2023
• Study Completion: May 11, 2023
• Last Updated: November 21, 2024
• Results First Posted: February 23, 2024

Record last verified: 2024-11

Locations

US (1)