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

Phase 2

Completed

• Conditions: Metastatic Triple Negative Breast Cancer
• Interventions: Drug: Tumor infiltrating lymphocytes (TIL) LN-145

• Registration Number: NCT04111510
• Lead Sponsor: Yale University

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 Timeline

• Study First Submitted: 2019-09-30
• Study First Submitted QC: 2019-09-30
• Study First Posted: 2019-10-01
• Study Start: 2019-12-23
• Primary Completion: 2023-01-30
• Study Completion: 2023-05-11
• Results First Submitted: 2024-01-29
• Results First Submitted QC: 2024-01-29
• Results First Posted: 2024-02-23
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-14
• Last Update Posted: 2024-11-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

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 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.

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

• Patients must have a washout period of 21 days from last anticancer therapy prior to the first study treatment (ie, start of NMA LD).

• Palliative radiation therapy: prior external beam radiation is allowed provided all radiation-related toxicities are resolved to Grade 1 or baseline;

  • The tumor lesion(s) being assessed as target for response via RECIST 1.1 must be outside of the radiation portal (however, if within the portal, they must have demonstrated progression);
  • Surgery/pre-planned procedure: previous surgical procedure(s) is permitted provided that wound healing has occurred, all complications have resolved, and at least 14 days have elapsed (for major operative procedures) prior to the tumor resection.

• 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).

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to 4 months	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.
Safety Profile	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). Incidence is presented as a count of participants that experienced at least 1 TEAE of Grade ≥ 3.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR) in Days	Up to 3 years	To evaluate the efficacy of autologous LN-145 as a single therapy in Metastatic Triple Negative Breast Cancer patients in participants that have a clinical response (either partial response (PR) or complete response (CR)) using duration of response (DOR), using RECIST 1.1, as assessed by the Investigator will be used.
Disease Control Rate (DCR)	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. Percentage of patients whose disease shrinks or remains stable over a certain time period.
Progression-free Survival (PFS)	Up to 3 years	To evaluate the efficacy of autologous LN-145 as a single therapy in Metastatic Triple Negative Breast Cancer patients, median progression-free survival (PFS) days, using RECIST 1.1, as assessed by the Investigator will be used.
Overall Survival (OS)	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) median days will be used.
Complete Response (CR)	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. The number of participants with a complete response.

Trial Locations

Locations (1)

Yale School of Medicine; 🇺🇸 New Haven, Connecticut, United States