Neoplasms

All Conditions

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Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

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Thyroid Diseases

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Giant Cell Tumor of Bone

Histiocytoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

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Disease Attributes

Neoplasms, Connective and Soft Tissue

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Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

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Genital Diseases

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Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

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Urogenital Neoplasms

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Neoplasms, Fibrous Tissue

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Undifferentiated Pleomorphic Sarcoma

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All Drugs and Chemicals

Antineoplastic Agents

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Anti-Infective Agents

Analgesics

Amino Acids

Antibodies

Antibodies, Monoclonal

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Nivolumab

Ipilimumab

Immunoglobulins

Interleukin-2

Immunosuppressive Agents

Immunologic Factors

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Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Serine

Ipilimumab 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.

Patients 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.

Autologous Tumor Infiltrating Lymphocytes LN-145

Autologous Tumor Infiltrating Lymphocytes LN-145-S1

Quality-of-Life Assessment

Questionnaire Administration

Amir A Jazaeri

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.

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.

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

Determined by T-cell receptor (TCR) sequencing of infused T cells serially isolated following LN-145/LN-145-S1 infusion, or alternatively iRepertoire assessment of messenger ribonucleic acid for the TCRs.

Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 percentage \[%\], CD27 and CD28 expression, etc.) and response to therapy.

Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 %, CD27 and CD28 expression, etc.) and response to therapy.

Paired t-test will be used to examine the molecular and immunological features of tumors before and after TIL therapy.

Assessed per the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) questionnaire.

Assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Estimation will use 80% confidence intervals by the Wilson score method.

Will be summarized using Kaplan-Meier estimates.

Iovance Biotherapeutics, Inc.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for malignancy in giant cell tumor of bone