Clinical Trial 18959

• Overview

  Study Title:

  A Phase 2 Study to Evaluate the Safety, Tolerability and Efficacy of Cell Transfer Therapy Using Autologous Tumor Infiltrating Lymphocytes (LN-145) followed by IL-2 in Patients with Recurrent and/or Metastatic Cervical Carcinoma

  Summary:

  The purpose of this study is to find out if an investigational product called LN-145 is safe to give to participants with recurrent and/or metastatic cervical cancer and if processing tumors to obtain cells in a central lab works. LN-145 is also called tumor infiltrating lymphocytes (TILs). TILs are generated by processing the patient¿s own tumor in a lab to extract and grow specialized white cells called lymphocytes that may attack their tumor. LN-145 is an investigational drug. Investigational means that it has not been approved by the Food and Drug Administration (FDA). Other drugs used in this study although they may be approved for other conditions may be considered investigational in this study.

  Objective:

  Primary Objectives: - To evaluate the safety and tolerability of lymphodepletion, LN-145, and IL-2 in patients with recurrent and/or metastatic cervical carcinoma. - To evaluate the efficacy of therapy using the overall response rate (ORR) in patients with recurrent and/or metastatic cervical carcinoma. Secondary Objectives: - To evaluate other efficacy parameters such as complete response (CR) rate, the duration of response (DOR), progression-free survival (PFS), and overall survival (OS) in patients with recurrent and/or metastatic cervical carcinoma. Exploratory Objectives: - To explore persistence of TILs and immune correlates of response, survival, toxicity of the treatment.

• Treatments

  Therapies:

  Cell Therapy; Chemotherapy (NOS)

  Medications:

  Fluconazole (); IL-2 (Interleukin-2); LN-145 (); MESNA (); Neupogen (filgrastim); Pembrolizumab (Keytruda); cyclophosphamide (); cytoxan (cyclophosphamide); filgrastim (); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  Inclusion Criteria:
  • Must be greater than 18 years of age at the time of consent.
  • Must have recurrent, metastatic or persistent SSC, ASC, or AC of the cervix, which is not amenable to curative treatment with surgery and/or radiation therapy.
  • Must have at least one resectable lesion (or aggregate of lesions resected) of a minimum 1.5 cm in diameter post-resection to generate TIL; surgical removal with minimum morbidity (defined as any procedure for which expected hospitalization is > At least one measurable target lesion, as defined by RECIST v1.1.
  • Must have had progression during or following at least one and no more than three prior systemic chemotherapeutic treatments for recurrent, metastatic or pestistent cervical carcinoma.
  • A line of systemic therapy is defined as any chemotherapy or multiple-agent chemotherapy regimen that was administered for recurrent, metastatic or persistent SCC, ASC, or AC of the cervix
  • A bevacizumab and chemotherapy combination is encouraged as a prior line of treatment
  • Neither chemoradiation, nor chemotherapy in the neoadjuvant or adjuvant settings are considered as a prior line of systemic therapy
  • Any prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted agents and immunologic agents must be discontinued at least 28 days prior to tumor resection. Radiation therapy must have been completed at least 3 months prior to resection of TIL-generating lesion or at least 3 months prior to Baseline for target lesions. Radiation therapy permitted as long as the lesions irradiated are not expected to be used for TIL generation or as target lesions and any toxicities have resolved to Grade > Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Participant has no evidence of any active viral, bacterial, or fungal infection requiring ongoing systemic treatment. Participants must be seronegative for the HIV antibody.
  • Must meet laboratory criteria per protocol.
  • Participants of childbearing potential must be willing to practice an approved method of birth control starting at the time of informed consent and for 1 year after the completion of the study treatment regimen.
  • Additional criteria may apply

• Exclusion Criteria

  Exclusion Criteria:
  • Have received an organ allograft or prior cell transfer therapy, except for prior LN-145 therapy.
  • Participants who require systemic steroid therapy
  • Currently have prior therapy-related toxicities >Grade 1 according to NCI-CTCAE v5.0; except for peripheral neuropathy, alopecia or vitiligo prior to enrollment/ tumor resection. Patients with a history of uveitis must have an eye examination performed at Screening to rule out active uveitis that requires treatment. Patient who has active uveitis that requires active treatment will be excluded.
  • Documented Grade 2 or greater diarrhea or colitis as a result of previous immunotherapy (e.g., ipilimumab, tremelimumab, anti-PD-1 or anti-PD-L1) within 6 months from screening.
  • History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, IL-2, or aminoglycosides (e.g., gentamicin or streptomycin).
  • Patients with active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, including evidence in the medical history of a positive cardiac stress test, myocardial infarction, cardiac arrhythmia, or obstructive or restrictive pulmonary disease, or other conditions that in the opinion of the Investigator would increase the risk of participation..
  • Symptomatic and/or untreated brain metastases (of any size and any number).
  • Have any form of primary immunodeficiency, such as severe combined immunodeficiency disease or acquired immune deficiency syndrome (AIDS).
  • Diagnosis of end-stage renal disorder requiring hemodialysis.
  • Have a left ventricular ejection fraction (LVEF) 60 years of age or those with a prior history of clinically significant cardiac disease who have an abnormal cardiac stress test.
  • Have a FEV1 (forced expiratory volume in 1 second) of less than or equal to 60% of predicted normal.
  • Additional criteria may apply

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