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
2 other identifiers
interventional
30
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Apr 2018
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 22, 2018
CompletedFirst Posted
Study publicly available on registry
February 28, 2018
CompletedStudy Start
First participant enrolled
April 27, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2027
November 21, 2025
November 1, 2025
9 years
February 22, 2018
November 20, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Objective response rate
Assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Estimation will use 80% confidence intervals by the Wilson score method.
Up to 3 years
Secondary Outcomes (5)
Disease control rate
Up to 3 years
Duration of response
Up to 3 years
Progression free survival
Up to 3 years
Overall survival
Up to 3 years
Incidence of adverse events of adoptive cell therapy with tumor infiltrating lymphocytes (TIL) across multiple tumor types
Up to 3 years
Other Outcomes (5)
Duration of TIL persistence
Up to 3 years
Response as determined by the immune-related response criteria
Up to 3 years
Immunological phenotype of LN-145 by multichannel flow cytometry
Day 0
- +2 more other outcomes
Study Arms (2)
ICI Ovarian Cancer, Sarcomas, Triple Negative Breast Cancer (LN-145-S1, nivolumab)
EXPERIMENTALIpilimumab will be administered as a single dose prior to tumor resection. Nivolumab will be administered once prior to tumor resection. 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. The second dose will be administered prior to TIL administration and dosing will continue every 4 weeks and continued until unacceptable toxicity, progression, or start of another cancer therapy.
Thyroid Cohort (LN-145)
EXPERIMENTALPatients receive cyclophosphamide 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.
Interventions
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Ancillary studies
Ancillary studies
Eligibility Criteria
You may qualify if:
- Age between 18 and 70 (Subjects aged 16-70 may be enrolled into the osteosarcoma cohort).
- Subjects must be willing and able to provide informed consent. For patients \< 18 years of age, their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Subjects must have an area of tumor amenable to excisional biopsy (core biopsies may be allowed as detailed in protocol) for the generation of TIL separate from, and in addition to, a target lesion to be used for response assessment.
- Any prior therapy directed at the malignant tumor, including radiation therapy, chemotherapy, and biologic/targeted agents must be discontinued at least 28 days prior to enrollment for preparing TIL therapy. Palliative therapy may be received during the screening period with principal investigator (PI) approval for lesions that are not expected to be used for TIL generation or as target lesions.
- Absolute neutrophil count (ANC) \>= 1000/mm\^3 (within 7 days of enrollment).
- Hemoglobin \>= 8.0 g/dL (transfusion allowed) (within 7 days of enrollment).
- Platelet count \>= 100,000/mm\^3 (within 7 days of enrollment).
- Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) and aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) =\< 2.5 x the upper limit of normal (ULN)
- Patients with liver metastases may have liver function tests (LFT) =\< 5.0 x ULN (within 7 days of enrollment).
- Calculated creatinine clearance (Cockcroft-Gault) \>= 50.0 mL/min (within 7 days of enrollment).
- Total bilirubin =\< 1.5 x ULN (within 7 days of enrollment).
- Prothrombin time (PT) \& activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (correction with vitamin K allowed) unless subject is receiving anticoagulant therapy (which should be managed according to institutional norms prior to and after excisional biopsy) (within 7 days of enrollment)
- Negative serum pregnancy test (female subjects of childbearing potential) (within 7 days of enrollment)
- Subjects must not have a confirmed human immunodeficiency virus (HIV) infection.
- +30 more criteria
You may not qualify if:
- Active or uncontrolled intercurrent illness, including but not limited to ongoing or active infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system. Principal investigator (PI) or his/her designee shall make the final determination regarding appropriateness of enrollment.
- Patients with active viral hepatitis.
- Patients who have a left ventricular ejection fraction (LVEF) \< 45% at screening.
- Patients with a history of prior adoptive cell therapies.
- Persistent prior therapy-related toxicities greater than grade 2 according to Common Toxicity Criteria for Adverse Events (CTCAE) version (v)4.03, except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment.
- Patients who have had a documented grade 2 or greater diarrhea or colitis due to previous immunotherapy must have been asymptomatic for at least 6 months or had a normal colonoscopy post checkpoint treatment, by visual assessment, prior to enrollment.
- Patients with immunotherapy-related endocrinopathies (e.g. hypothyroidism or hypopituitarism, who are stable on hormonal substitution) and controlled with hormonal replacement, are allowed.
- Primary immunodeficiency.
- History of organ or hematopoietic stem cell transplant.
- Chronic steroid therapy, however prednisone or its equivalent is allowed at =\< 10 mg/day.
- Patients who are pregnant or nursing.
- Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his/her designee, would prevent adequate informed consent.
- History of clinically significant autoimmune disease including active, known, or suspected autoimmune disease. Subjects with resolved side effects from prior checkpoint inhibitor therapy, vitiligo, psoriasis, type 1 diabetes or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded.
- History of clinically significant chronic obstructive pulmonary disease (COPD), asthma, interstitial lung disease, or other chronic lung disease.
- History of known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to initiation of lymphodepletion.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- Iovance Biotherapeutics, Inc.collaborator
- National Cancer Institute (NCI)collaborator
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Amir A Jazaeri
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 22, 2018
First Posted
February 28, 2018
Study Start
April 27, 2018
Primary Completion (Estimated)
April 30, 2027
Study Completion (Estimated)
April 30, 2027
Last Updated
November 21, 2025
Record last verified: 2025-11