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Study of LN-145/LN-145-S1 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck

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ClinicalTrials.gov Identifier: NCT03083873
Recruitment Status : Recruiting
First Posted : March 20, 2017
Last Update Posted : January 28, 2020
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE March 14, 2017
First Posted Date  ICMJE March 20, 2017
Last Update Posted Date January 28, 2020
Actual Study Start Date  ICMJE January 9, 2017
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
Objective Response Rate [ Time Frame: Up to 24 months ]
To evaluate the efficacy of LN-145/LN-145-S1 in patients with recurrent and/or metastatic HNSCC based on the objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the Investigator
Original Primary Outcome Measures  ICMJE
 (submitted: March 14, 2017)
  • Adverse Events [ Time Frame: 12 months ]
    Incidence of treatment-emergent AEs (TEAEs), including SAEs, therapy-related AEs, AEs leading to early discontinuation of treatment or withdrawal from the study or death
  • Objective Response Rate [ Time Frame: Up to 24 months ]
    To evaluate the efficacy of therapy based on objective response rate
Change History Complete list of historical versions of study NCT03083873 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
  • Duration of Response [ Time Frame: Up to 24 months ]
    To evaluate efficacy parameters such as Duration of Response (DOR) using RECIST v1.1 as assessed by the Investigator
  • Disease Control Rate [ Time Frame: Up to 24 months ]
    To evaluate efficacy parameters such as Disease Control Rate (DCR) using RECIST v1.1 as assessed by the Investigator
  • Progression-Free Survival [ Time Frame: Up to 24 months ]
    To evaluate efficacy parameters such as Progression-Free Survival (PFS) using RECIST v1.1 as assessed by the Investigator
  • Overall Survival [ Time Frame: Up to 36 months ]
    To evaluate Overall Survival (OS) in patients with recurrent and/or metastatic HNSCC
  • Safety Profile as Assessed by Incidence of Adverse Events [ Time Frame: Up to 24 months ]
    To characterize the safety profile of LN-145/LN-145-S1 in patients with metastatic and/or recurrent HNSCC
Original Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2017)
  • Complete Response Rate [ Time Frame: Up to 24 months ]
    To evaluate efficacy parameters such Complete Response (CR) rate
  • Duration of Response [ Time Frame: Up to 24 months ]
    To evaluate efficacy parameters such Duration of Response (DOR)
  • Progression-Free Survival [ Time Frame: Up to 24 months ]
    To evaluate efficacy parameters such Progression-Free Survival (PFS)
  • Overall Survival [ Time Frame: Up to 24 months ]
    To evaluate efficacy parameters such Overall Survival (OS)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of LN-145/LN-145-S1 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck
Official Title  ICMJE A Phase 2, Multicenter Study to Evaluate the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-145/LN-145-S1) for the Treatment of Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck
Brief Summary Multicenter, multicohort, non-randomized, prospective, open label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor infiltrating lymphocytes (TIL) infusion (LN-145/LN-145-S1) followed by IL-2 after a non-myeloablative (NMA) lymphodepletion preparative regimen for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck
Detailed Description LN-145/LN-145-S1 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI, for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. The cell transfer therapy used in this study involves patients receiving a NMA lymphocyte depleting preparative regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Squamous Cell Carcinoma of the Head and Neck
Intervention  ICMJE
  • Biological: LN-145
    A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.
    Other Name: TIL, autologous tumor infiltrating lymphocytes
  • Biological: LN-145-S1
    A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with autologous TIL (LN-145-S1) followed by IL-2 administration.
    Other Name: TIL, autologous tumor infiltrating lymphocytes
Study Arms  ICMJE
  • Experimental: Cohort 1
    Treatment with LN-145, Generation 1 (Gen 1), non-cryopreserved TIL
    Intervention: Biological: LN-145
  • Experimental: Cohort 2
    Treatment with LN-145 Generation 2 (Gen 2), cryopreserved TIL
    Intervention: Biological: LN-145
  • Experimental: Cohort 3
    Treatment with LN-145 Generation 3 (Gen 3), cryopreserved TIL
    Intervention: Biological: LN-145
  • Experimental: Cohort 4
    Treatment with LN-145-S1 cryopreserved TIL
    Intervention: Biological: LN-145-S1
  • Experimental: Cohort 5
    LN-145 cryopreserved/LN-145-S1 cryopreserved TIL re-treatment
    Interventions:
    • Biological: LN-145
    • Biological: LN-145-S1
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 24, 2020)
55
Original Estimated Enrollment  ICMJE
 (submitted: March 14, 2017)
47
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Must be greater than 18 years of age at the time of consent.
  • Must have recurrent and/or metastatic, squamous cell carcinoma of the head and neck (both HPV-positive and -negative)
  • Must have at least 1 lesion that is resectable for TIL generation.
  • Must have measurable disease as defined by RECIST v1.1 following the surgical resection.
  • Must have received at least 1 and no more than 3 lines of prior systemic immunotherapy and/or chemotherapeutic treatments for HNSCC.
  • Any prior therapy directed at the malignant tumor must be discontinued at least 28 days prior to lymphodepletion.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Patients must be seronegative for the human immunodeficiency virus.
  • Patients seropositive for hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), or hepatitis C virus (anti-HCV) indicating acute or chronic infection may be enrolled if the viral load by polymerase chain reaction (PCR) is undetectable with/without active treatment
  • Patients of childbearing potential and patients whose sexual partners are of childbearing potential must be willing to practice an approved method of highly effective birth control starting at the time of informed consent and for 1 year after the completion of the study treatment regimen.

Exclusion Criteria:

  • Patients who have received an organ allograft or prior cell transfer therapy within the past 20 years.
  • Patients who are on a systemic steroid therapy (greater than 10 mg of prednisone or equivalent). Patients receiving steroids as replacement therapy for adrenocortical insufficiency at < 10 mg of prednisone or other steroid equivalent daily may be eligible.
  • Prior therapy-related toxicities Grade ≥ 1 according to Common Toxicity Criteria for Adverse Events (CTCAE) v4.03
  • Patients with documented Grade ≥ 2 diarrhea or colitis as a result of previous immunotherapy within six months from screening.
  • Patients who have a contraindication to or history of hypersensitivity reaction to cyclophosphamide, mesna, fludarabine, IL-2, antibiotics of the aminoglycoside group (ie, gentamicin or streptomycin; excluding those who are skin-test negative for gentamicin hypersensitivity), any component of the TIL infusion product formulation including dimethylsulfoxide (DMSO), human serum albumin (HSA), IL-2, and dextran-40.
  • Patients with active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system.
  • Patients with symptomatic and/or untreated brain metastases.
  • Have any form of primary or acquired immunodeficiency syndrome, such as severe combined immunodeficiency disease or acquired immune deficiency syndrome (AIDS).
  • Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association (NYHA) Class 2 or higher.
  • Patients who have had another primary malignancy within the previous 3 years.
  • Patients who are pregnant, parturient, or breastfeeding women.
  • Patients who have received a live or attenuated vaccine within 28 days of the NMA-LD regimen.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Iovance Biotherapeutics Study Team 866-565-4410 Clinical.Inquiries@iovance.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03083873
Other Study ID Numbers  ICMJE C-145-03
2016-003446-86 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Iovance Biotherapeutics, Inc.
Study Sponsor  ICMJE Iovance Biotherapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Iovance Biotherapeutics Medical Monitor Iovance Biotherapeutics
PRS Account Iovance Biotherapeutics, Inc.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP