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JOURNAL ONKOLOGIE – STUDIE

Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors

Rekrutierend

NCT-Nummer:
NCT03645928

Studienbeginn:
Mai 2019

Letztes Update:
01.04.2021

Wirkstoff:
Lifileucel, LN-145, Pembrolizumab, LN-145-S1, Ipilimumab, Nivolumab

Indikation (Clinical Trials):
Squamous Cell Carcinoma of Head and Neck

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Iovance Biotherapeutics, Inc.

Collaborator:
-

Studienleiter

Iovance Biotherapeutics Medical Monitor
Study Director
Iovance Biotherapeutics

Kontakt

Iovance Biotherapeutics Study Team
Kontakt:
Phone: 866-565-4410
E-Mail: Clinical.Inquiries@iovance.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 40)

University of California, San Diego
92093 La Jolla
United StatesRekrutierend» Google-Maps
University of Southern California
90007 Los Angeles
United StatesRekrutierend» Google-Maps
University of California, Los Angeles
90095 Los Angeles
United StatesRekrutierend» Google-Maps
Georgetown University Medical Center
20007 Washington
United StatesRekrutierend» Google-Maps
Mount Sinai Medical Center
33140 Miami Beach
United StatesZurückgezogen» Google-Maps
University of Louisville
40292 Louisville
United StatesRekrutierend» Google-Maps
University of Maryland
21201 Baltimore
United StatesRekrutierend» Google-Maps
Massachusetts General Hospital
02114 Boston
United StatesRekrutierend» Google-Maps
Karmanos Cancer Institute
48201 Detroit
United StatesRekrutierend» Google-Maps
Henry Ford Health System
48202 Detroit
United StatesRekrutierend» Google-Maps
Morristown Medical Center
07960 Morristown
United StatesRekrutierend» Google-Maps
Memorial Sloan Kettering Cancer Center
10065 New York
United StatesRekrutierend» Google-Maps
University of Cincinnati
45219 Cincinnati
United StatesRekrutierend» Google-Maps
Ohio State University
43201 Columbus
United StatesRekrutierend» Google-Maps
Huntsman Cancer Hospital
84112 Salt Lake City
United StatesRekrutierend» Google-Maps
Fred Hutchinson Cancer Research Center
98109 Seattle
United StatesRekrutierend» Google-Maps
Medical College of Wisconsin
53226 Milwaukee
United StatesRekrutierend» Google-Maps
Princess Margaret Cancer Centre
M5G 2C1 Toronto
CanadaRekrutierend» Google-Maps
Laiko General Hospital of Athens
11527 Athens
GreeceRekrutierend» Google-Maps
Attikon University General Hospital
12461 Athens
GreeceRekrutierend» Google-Maps
Hospital Universitario Marques de Valdecilla
39008 Santander
SpainRekrutierend» Google-Maps
University Hospital Vall d'Hebron
08035 Barcelona
SpainRekrutierend» Google-Maps
ICO l'Hospitalet - Hospital Duran i Reynals
08908 Barcelona
SpainRekrutierend» Google-Maps
Hospital General Universitario Gregorio Marañón
28007 Madrid
SpainRekrutierend» Google-Maps
Hospital Universitario Fundacion Jimenez Diaz
28040 Madrid
SpainRekrutierend» Google-Maps
Hospital Universitario 12 de Octubre
28041 Madrid
SpainRekrutierend» Google-Maps
Hospital Universitario HM Sanchinarro
28050 Madrid
SpainRekrutierend» Google-Maps
Hospital Regional Universitario de Malaga - Hospital General
29016 Málaga
SpainRekrutierend» Google-Maps
Centre Hospitalier Universitaire Vaudois
1011 Lausanne
SwitzerlandRekrutierend» Google-Maps
Bristol Haematology and Oncology Centre
BS2 8ED Bristol
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

LN-144 (Lifileucel)/LN-145/LN-145-S1 is an adoptive cell transfer therapy that utilizes an

autologous TIL for the treatment of patients with unresectable or metastatic melanoma,

advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, and locally

advanced or metastatic non-small cell lung cancer. The adoptive cell transfer therapy used in

this study involves patients receiving a nonmyeloablative (NMA) lymphodepletion regimen,

followed by infusion of autologous TIL followed by the administration of a regimen of IL-2.

Patients in Cohorts 1A, 2A, 3A and 3C will receive TIL plus checkpoint inhibitors. Patients

in Cohorts 1B, 1C, and 3B will receive autologous TIL as a single therapy.

Ein-/Ausschlusskriterien

Inclusion Criteria

- Must have a confirmed diagnosis of malignancy of their receptive histologies:

unresectable or metastatic melanoma Stage IIIC or Stage IV (Cohorts 1A,1B and 1C),

advanced, recurrent or metastatic HNSCC (Cohort 2A), or Stage III or Stage IV

non-small cell lung cancer (Cohorts 3A, 3B, and 3C).

- Cohorts 1A, 2A, and 3A: If previously treated, patients must have progressed on or

after most recent therapy and must not have received CPIs as part of one of the

counted lines of prior therapy. Patients must have radiologically documented disease

progression while receiving or after the completion of the most recent prior

treatment. Patients may have received up to 3 prior systemic anticancer therapies

(except for Cohort 3A, where patients whose tumors harbor actionable mutations may

have received up to 4 prior systemic therapies)

- Cohorts 1B, 1C, 3B, and 3C: Metastatic melanoma patients in Cohorts 1B or 1C must have

previously received systemic therapy with a PD-1 blocking antibody. NSCLC patients in

Cohort 3B must have previously received systemic therapy with any CPI (except for

those patients with known oncogene drivers (eg, EGFR, ALK, ROS) who have mutations

that are sensitive to targeted therapies) as part of 1 - 3 prior lines of therapy.

NSCLC patients in Cohort 3C must have received prior systemic therapy with an approved

monotherapy CPI as their single prior line of systemic therapy.

- Must have at least 1 resectable lesion

- Must have a remaining measurable disease as defined by RECIST 1.1 following tumor

resection

- Must be ≥ 18 years at the time of consent for Cohorts 1A, 1C, 2A, 3A, 3B, and 3C.

Patients must be ≥ 12 years at the time of consent for Cohort 1B. Enrollment of

patients > 70 years of age may be allowed after consultation with the Medical Monitor.

- Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1,

and an estimated life expectancy of ≥ 6 months.

- Patients of childbearing potential or those with partners of childbearing potential

must be willing to practice an approved method of birth control during treatment and

for 12 months after receiving all protocol-related therapy.

Exclusion Criteria

- Patients with melanoma of uveal/ocular origin.

- Patients who have received an organ allograft or prior cell transfer therapy that

included a nonmyeloablative or myeloablative chemotherapy regimen within the past 20

years.

- Patients with symptomatic and/or untreated brain metastases

- Patients who are on systemic steroid therapy ≥ 10 mg/day of prednisone or other

steroid equivalent. Patients receiving steroids as replacement therapy for

adrenocortical insufficiency at ≤ 10 mg/day of prednisone or other steroid equivalent

may be eligible.

- Patients who are pregnant or breastfeeding.

- Patients who have an active medical illness(es), which in the opinion of the

Investigator, would pose increased risks for study participation

- Cohort 1A, 2A, 3A, and 3C patients may not have a medical history of autoimmune

disorders requiring treatment or active management.

- Patients who have received a live or attenuated vaccination within 28 days prior to

the start of treatment

- Patients who have any form of primary immunodeficiency

- Patients with a history of hypersensitivity to any component of the study drugs

- Patients who have a left ventricular ejection fraction (LVEF) > 45% or who are New

York Heart Association Class II or higher

- Patients with respiratory dysfunction or history of smoking are excluded if not

meeting either of forced expiratory volume in 1 second (FEV1)/forced vital capacity

(FVC) > 0.7 or FEV1 > 50%.

- Patients who have had another primary malignancy within the previous 3 years

- Participation in another interventional clinical study within 21 days of the

initiation of treatment.

Studien-Rationale

Primary outcome:

1. Objective Response Rate (Time Frame - Up to 60 months):
To evaluate the efficacy of autologous TIL in combination with CPIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients (who have previously progressed on or after treatment with a PD-1 blocking antibody for metastatic melanoma), as determined by objective response rate (ORR), using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as assessed by Investigator

2. Safety Profile Measured by Grade ≥3 TEAEs (Time Frame - Up to 60 months):
To characterize the safety profile of autologous TIL in combination with CPIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients as measured by the incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs)

Secondary outcome:

1. Complete Response Rate (Time Frame - Up to 60 months):
To evaluate efficacy parameters such Complete Response (CR) rate per RECIST 1.1, as assessed by the Investigator

2. Duration of Response (Time Frame - Up to 60 months):
To evaluate efficacy parameters such Duration of Response (DOR) per RECIST 1.1, as assessed by the Investigator

3. Disease Control Rate (Time Frame - Up to 60 months):
To evaluate efficacy parameters such Disease Control Rate (DCR) per RECIST 1.1, as assessed by the Investigator

4. Progression-Free Survival (Time Frame - Up to 60 months):
To evaluate efficacy parameters such Progression-Free Survival (PFS) per RECIST 1.1, as assessed by the Investigator

5. Overall Survival (Time Frame - Up to 60 months):
To evaluate efficacy parameters such Overall Survival (OS)

Studien-Arme

  • Experimental: Cohort 1A
    LN-144 therapy in combination with pembrolizumab in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma with ≤ 3 prior lines of systemic therapy, excluding checkpoint inhibitors (CPI).
  • Experimental: Cohort 1B
    LN-145-S1 therapy as a single agent in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is proto-oncogene B-Raf (BRAF) V600 mutation positive, patients must have received a BRAF inhibitor or BRAF inhibitor in combination with or without a mitogen-activated extracellular signal-related kinase (MEK) inhibitor.
  • Experimental: Cohort 1C
    LN-144 Generation 3 (Gen 3) therapy as a single agent in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is BRAF V600 mutation positive, patients must have received BRAF inhibitor with or without a MEK inhibitor.
  • Experimental: Cohort 2A
    LN-145 therapy in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding CPIs.
  • Experimental: Cohort 3A
    LN-145 therapy in combination with pembrolizumab in patients with locally advanced or metastatic (Stage III or Stage IV) non-small-cell lung cancer (NSCLC) with ≤ 3 prior lines of systemic therapy, excluding CPIs or ≤ 4 prior lines if 2 or more of the lines are TKI therapy for those with tumors that harbored actionable mutations (eg, EGFR, ALK, ROS).
  • Experimental: Cohort 3B
    LN-145 therapy as a single agent in patients with Stage III or Stage IV NSCLC, who have previously received 1-3 lines of prior systemic therapy. Patients with known oncogene drivers (eg, EGFR, ALK, ROS) who have mutations that are sensitive to targeted therapies are not required to have received prior systemic therapy with CPIs.
  • Experimental: Cohort 3C
    LN-145 therapy in combination with ipilimumab and nivolumab in patients with Stage III or Stage IV NSCLC who have previously received 1 line of approved CPI monotherapy as the only prior line of systemic therapy.

Geprüfte Regime

  • Lifileucel (LN-144, TIL, autologous tumor infiltrating lymphocytes, lifileucel):
    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 Lifileucel followed by IL-2 administration. Lifileucel will be administered to patients once (on Day 0) during the study.
  • LN-145 (TIL, autologous tumor infiltrating lymphocytes):
    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. TIL will be administered to patients once (on Day 0) during the study.
  • Pembrolizumab (Keytruda):
    Humanized antibody. Pembrolizumab will be administered following tumor resection and will continue every 3 weeks or every 6 weeks thereafter for up to 2 years.
  • LN-145-S1 (TIL, autologous tumor infiltrating lymphocytes):
    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-S1) followed by IL-2 administration. TIL will be administered to patients once (on Day 0) during the study.
  • Ipilimumab (Yervoy):
    Monoclonal antibody Ipilimumab will be administered as a single dose prior to tumor resection.
  • Nivolumab (Opdivo):
    Monoclonal antibody Nivolumab will be administered once prior to tumor resection. The second dose will be administered prior to TIL administration and dosing will continue every 4 weeks for up to 2 years.

Quelle: ClinicalTrials.gov


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