Trials / Active Not Recruiting

Active Not RecruitingNCT03449108

LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas

Clinical Study to Assess Efficacy and Safety of LN-145/LN-145-S1 (Autologous Centrally Manufactured Tumor Infiltrating Lymphocytes) Across Multiple Tumor Types

Status: Active Not Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 30 (actual)

Sponsor: M.D. Anderson Cancer Center · Academic / Other
Sex: All
Age: 16 Years – 70 Years
Healthy volunteers: Not accepted

Summary

This phase II trial studies how well autologous tumor infiltrating lymphocytes LN-145 (LN-145) or LN-145-S1 works in treating patients with ovarian cancer, triple negative breast cancer (TNBC), anaplastic thyroid cancer, osteosarcoma, or other bone and soft tissue sarcomas that do not respond to treatment (refractory) or that has come back (relapsed). LN-145 is made by collecting and growing specialized white blood cells (called T-cells) that are collected from the patient's tumor. LN-145-S1 is made using a modified process that chooses a specific portion of the T-cells. The T cells may specifically recognize, target, and kill the tumor cells.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate efficacy using objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in each cohort. SECONDARY OBJECTIVES: I. Determine the disease control rate (DCR) within and across cohorts. II. Determine the duration of response (DOR). III. Determine progression-free survival (PFS) and overall survival (OS). IV. Further characterize the safety profile of adoptive cell therapy with tumor infiltrating lymphocytes (TIL) across multiple tumor types. EXPLORATORY OBJECTIVES: I. Establish duration of tumor-infiltrating lymphocyte (TIL) persistence. II. Compare the molecular and immunological features of tumors before and after TIL therapy. III. Prospectively evaluate the existing immunotherapy response criteria (immune-related \[ir\]RECIST) as the best response assessment tool for TIL therapy among a diverse group of solid tumors. IV. To investigate TIL attributes (CD8 percentage \[%\], CD27 and CD28 expression) and correlation with response to therapy. V. Assess tumor marker (CA-125) response in patients who produce this tumor marker. VI. To assess Health-Related Quality of Life (HRQOL). OUTLINE: Patients are assigned to 1 of 2 cohorts. THYROID CANCER COHORT: Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, autologous tumor infiltrating lymphocytes LN-145 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses. ICI OVARIAN CANCER, OSTEOSARCOMA, Triple Negative Breast Cancer, or OTHER BONE AND SOFT TISSUE SARCOMAS COHORT: Within 2-4 weeks prior to surgery, patients receive a single dose of nivolumab IV over 30 minutes, followed by a single dose of ipilimumab IV over 30 minutes Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, LN-145-S1 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses. Within 12 weeks after receiving LN-145-S1, patients receive nivolumab IV over 30 minutes every 4 weeks in the absence of disease progression or unacceptable toxicity. For cohorts treated without immune checkpoint inhibitors, completion of treatment is defined as having received any volume of LN-145/LN-145-S1 infusion followed by at least 1 dose of adjuvant IL-2. For cohorts treated with TIL + ICI, completion of treatment will correspond to the last dose of nivolumab or IL2 (if the subject is deemed unsuitable to receive adjuvant nivolumab). Patients are followed up at 18 weeks, 6, 9, 12, 18 and 24 months, then every 3 months for at least 3 years.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Aldesleukin	Given IV
BIOLOGICAL	Autologous Tumor Infiltrating Lymphocytes LN-145	Given IV
BIOLOGICAL	Autologous Tumor Infiltrating Lymphocytes LN-145-S1	Given IV
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine	Given IV
BIOLOGICAL	Ipilimumab	Given IV
BIOLOGICAL	Nivolumab	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies

Timeline

Start date: 2018-04-27
Primary completion: 2027-04-30
Completion: 2027-04-30
First posted: 2018-02-28
Last updated: 2025-11-21

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03449108. Inclusion in this directory is not an endorsement.