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JOURNAL ONKOLOGIE – STUDIE

Study of LN-145, Autologous Tumor Infiltrating Lymphocytes in the Treatment of Patients With Cervical Carcinoma

Rekrutierend

NCT-Nummer:
NCT03108495

Studienbeginn:
Juni 2017

Letztes Update:
09.06.2021

Wirkstoff:
LN-145, LN-145 + pembrolizumab

Indikation (Clinical Trials):
Carcinoma

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Iovance Biotherapeutics, Inc.

Collaborator:
-

Studienleiter

Iovance Medical Monitor
Study Director
Iovance Biotherapeutics, Inc.

Kontakt

Iovance Biotherapeutics Clinical Inquiries
Kontakt:
Phone: 650-260-7120
E-Mail: Clinical.Inquiries@iovance.com
» Kontaktdaten anzeigen
Iovance Biotherapeutics Clinical Inquiries
Kontakt:
Phone: 866-565-4410
E-Mail: Clinical.Inquiries@iovance.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 40)

Hautkrebszentrum Universitätsklinikum Erlangen
Ulmenweg 18
91054 Erlangen
(Bayern)
DeutschlandAktiv, nicht rekrutierend» Google-Maps
Universitätsklinikum Carl Gustav Carus
01307 Dresden
(Sachsen)
GermanyAktiv, nicht rekrutierend» Google-Maps
St. Joseph's Hospital and Medical Center Center For Women's Health
85013 Phoenix
United StatesRekrutierend» Google-Maps
University of Southern California
90033 Los Angeles
United StatesRekrutierend» Google-Maps
University of California San Diego
92093 San Diego
United StatesRekrutierend» Google-Maps
Sylvester Comprehensive Cancer Center
33136 Miami
United StatesRekrutierend» Google-Maps
University of Florida Health Cancer Center
32806 Orlando
United StatesRekrutierend» Google-Maps
University of South Florida H. Lee Moffitt Cancer Center and Research Institute
33612 Tampa
United StatesRekrutierend» Google-Maps
Augusta University
30912-0003 Augusta
United StatesRekrutierend» Google-Maps
James Graham Brown Cancer Center
40202 Louisville
United StatesRekrutierend» Google-Maps
LSU Health Sciences Center
70112 New Orleans
United StatesRekrutierend» Google-Maps
Dana Farber Cancer Institute
02215 Boston
United StatesRekrutierend» Google-Maps
Roswell Park Cancer Institute
14263 Buffalo
United StatesRekrutierend» Google-Maps
The Ohio State University Comprehensive Cancer Center
43210 Columbus
United StatesRekrutierend» Google-Maps
University of Oklahoma Health Sciences Center
73104 Oklahoma City
United StatesRekrutierend» Google-Maps
MD Anderson Cancer Center
77030 Houston
United StatesRekrutierend» Google-Maps
Medical College of Wisconsin
53225 Milwaukee
United StatesRekrutierend» Google-Maps
Centre Hospitalier Lyon Sud
69495 Pierre Bénite
FranceAktiv, nicht rekrutierend» Google-Maps
Gustave Roussy Cancer Campus
94805 Villejuif Cedex
FranceAktiv, nicht rekrutierend» Google-Maps
Istituto Europeo di Oncologia
20141 Miano
ItalyAktiv, nicht rekrutierend» Google-Maps
Academisch Medisch Centrum
1105 Amsterdam
NetherlandsAktiv, nicht rekrutierend» Google-Maps
Clínica Universidad de Navarra
31008 Pamplona
SpainAktiv, nicht rekrutierend» Google-Maps
Hospital Universitari Vall d'Hebrón
08035 Barcelona
SpainAktiv, nicht rekrutierend» Google-Maps
Institut Català d'Oncologia
08908 Barcelona
SpainAktiv, nicht rekrutierend» Google-Maps
Hospital General Universitario Gregorio Marañon
28007 Madrid
SpainAktiv, nicht rekrutierend» Google-Maps
Hospital Universitario Madrid Sanchinarro
28050 Madrid
SpainAktiv, nicht rekrutierend» Google-Maps
Centre Hospitalier Universitaire Vaudois Lausanne - Centre Pluridisciplinaire d'Oncologie
Lausanne
SwitzerlandAktiv, nicht rekrutierend» Google-Maps
Bristol Haematology and Oncology Centre
BS2 8ED Bristol
United KingdomAktiv, nicht rekrutierend» Google-Maps
Sarah Cannon Research Institute London
W1G 6AD London
United KingdomAktiv, nicht rekrutierend» Google-Maps
University College London Hospitals NHS Foundation Trust
W1G 6BW London
United KingdomAbgebrochen» Google-Maps
NHS Greater Glasgow and Clyde
G12 0YN Glasgow
United KingdomAktiv, nicht rekrutierend» Google-Maps
Guy's & St.Thomas NHS Foundation Trust
SE1 9RT London
United KingdomAktiv, nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

LN-145 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,

metastatic, or persistent cervical carcinoma. 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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

To be eligible for the study, patients must meet ALL of the following criteria prior to

participation:

1. Must be ≥ 18 years of age at the time of consent

Enrollment of patients > 70 years of age may be allowed after consultation with the

Medical Monitor.

2. Must have recurrent, metastatic, or persistent squamous cell carcinoma, adenosquamous

carcinoma, or adenocarcinoma of the cervix that is not amenable to curative treatment

with surgery and/or radiation therapy

3. 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 minimal morbidity

(defined as any procedure for which expected hospitalization is ≤ 3 days)

4. At least one measurable target lesion, as defined by RECIST v1.1

5. Cohort 1 and Cohort 2: Progression during or following at least one, but no more than

three, prior systemic chemotherapeutic treatments (such as carboplatin/cisplatin,

paclitaxel, and bevacizumab except where there are contraindications) for recurrent,

metastatic or persistent 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.

Cohort 2: Must also have previously received treatment with a checkpoint inhibitor

(ie, PD-1, PD-L1])

Cohort 3: Must have not received any therapies other than prior chemoradiation or

surgery for loco-regional disease

6. Any prior therapy directed at the malignant tumor must be discontinued at least 28

days prior to tumor resection. Radiation therapy may have been received up to 28 days

prior to tumor resection for lesions not expected to be used for TIL generation or

target lesions.

7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

8. Patients must be seronegative for the human immunodeficiency virus (HIV). Patients

with positive serology for hepatitis B virus surface antigen (HBsAg), hepatitis B core

antibody (anti-HBc), or hepatitis C virus antibody (HCV Ab) indicating acute or

chronic infection may be enrolled if the viral load by polymerase chain reaction (PCR)

is undetectable with/without active treatment.

9. Patients of childbearing potential must be willing to take the appropriate precaution

to avoid pregnancy for the duration of the study and practice an approved, highly

effective method of birth control during treatment and for 12 months after receiving

the last protocol-related therapy.

10. Prior to study Enrollment (tumor resection), patient must have documentation of

radiological disease progression after the most recent therapy.

Exclusion Criteria:

1. Patients who have received an organ allograft or prior cell transfer therapy except

for prior LN-145 therapy in the setting of re-treatment only.

2. Patients who are on chronic systemic steroid therapy

3. Patients who currently have prior therapy-related toxicities Grade > 1 according to

National Cancer Institute (NCI-) Common Terminology Criteria for Adverse Events

(CTCAE) v5.0; except for peripheral neuropathy, alopecia, or vitiligo prior to

Enrollment (tumor resection)

• Patients may not have any pre-planned procedures within 2 weeks prior to the start

of NMA-LD preparative regimen

4. Patients who have a history of hypersensitivity to any component or excipient of

LN-145 or other study drugs:

• NMA-LD preparative regimen (cyclophosphamide, mesna, and fludarabine)

5. Patients who have active systemic infections, coagulation disorders or other active

major medical illnesse(es) of the cardiovascular, respiratory, or immune system,

including evidence in the medical history of urinary tract obstruction, a positive

cardiac stress test, myocardial infarction, cardiac arrhythmia, obstructive or

restrictive pulmonary disease, or other conditions that in the opinion of the

Investigator would increase the risk of participation

6. Patients with symptomatic and/or untreated brain metastases (of any size and any

number)

• Patients with definitively treated brain metastases may be considered for

Enrollment, and must be stable for ≥ 14 days prior to beginning the NMA-LD preparative

regimen

7. Patients who have any form of primary immunodeficiency (such as severe combined

immunodeficiency [SCID] or acquired immunodeficiency syndrome [AIDS])

8. Patients who have a diagnosis of end-stage renal disorder requiring hemodialysis.

9. Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New

York Heart Association (NYHA) Class 2 or higher.

10. Patients who have a documented forced expiratory volume in 1 second (FEV1) of ≤ 60%

11. Patients who have had another primary malignancy within the previous 3 years (except

for curatively treated localized malignancy that has not required treatment for > 1

year, and in the judgement of the Investigator, does not pose a significant risk of

recurrence including, but not limited to, non-melanoma skin cancer or bladder cancer)

12. Patients who have received a live or attenuated vaccine within 28 days prior to

beginning NMA-LD preparative regimen.

13. Patients whose cancer requires immediate attention or who would otherwise suffer a

disadvantage by participating in this study

14. Cohort 1 and Cohort 3: Patients who have received prior treatment with immunotherapy

(eg, PD-1, PD-L1, or anti-cytotoxic T lymphocyte-associated antigen-4 [CTLA-4]

antibodies)

15. Patients who have Grade ≥ 2 hemorrhage within 14 days prior to Enrollment (tumor

resection)

16. Cohort 3: Patients may not have active or prior documented autoimmune or inflammatory

disorders (including pneumonitis, inflammatory bowel disease [eg, colitis or Crohn's

disease], diverticulitis [with the exception of diverticulosis], systemic lupus

erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with

polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]).

Studien-Rationale

Primary outcome:

1. Cohort 1 and 2: Objective Response Rate (Time Frame - Up to 6 months):
To evaluate the efficacy of LN-145 in patients with recurrent, metastatic, or persistent cervical carcinoma based on the objective response rate (ORR) as assessed by the Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

2. Cohort 3: Adverse Events (Time Frame - Up to 60 months):
To characterize the safety profile of LN-145 in combination with pembrolizumab in patients with recurrent, metastatic, or persistent cervical carcinoma as assessed by incidence of adverse events.

3. Cohort 4: Efficacy and Adverse Events (Time Frame - Up to 60 months):
To explore the efficacy and safety profile of LN-145 in previously enrolled patients with recurrent, metastatic, or persistent cervical carcinoma

4. Cohort 5: Efficacy and Adverse Events (Time Frame - Up to 60 months):
To explore the efficacy and safety profile of LN-145 in re-treated patients with recurrent, metastatic, or persistent cervical carcinoma

Secondary outcome:

1. Cohort 1 and 2: Duration of Response (Time Frame - Up to 60 months):
To evaluate the efficacy parameters of LN-145 in patients with recurrent, metastatic, or persistent cervical carcinoma by assessing duration of response (DOR) as assessed by the IRC per RECIST v1.1

2. Cohort 1 and 2: Disease Control Rate (Time Frame - Up to 60 months):
To evaluate the efficacy parameters of LN-145 in patients with recurrent, metastatic, or persistent cervical carcinoma by assessing disease control rate (DCR) as assessed by the IRC per RECIST v1.1

3. Cohort 1 and 2: Progression-Free Survival (Time Frame - Up to 60 months):
To evaluate the efficacy parameters of LN-145 in patients with recurrent, metastatic, or persistent cervical carcinoma by assessing progression-free survival (PFS) as assessed by the IRC per RECIST v1.1

4. Cohort 1 and 2: Objective Response Rate (Time Frame - Up to 60 months):
To evaluate the efficacy of LN-145 in patients with recurrent, metastatic, or persistent cervical carcinoma based on the objective response rate (ORR) as assessed by the Investigator per RECIST v1.1

5. Cohort 1 and 2: Duration of Response (Time Frame - Up to 60 months):
To evaluate the efficacy of LN-145 in patients with recurrent, metastatic, or persistent cervical carcinoma by assessing duration of response (DOR) as assessed by the Investigator per RECIST v1.1

6. Cohort 1 and 2: Disease Control Rate (Time Frame - Up to 60 months):
To evaluate the efficacy of LN-145 in patients with recurrent, metastatic, or persistent cervical carcinoma by assessing disease control rate (DCR) as assessed by the Investigator per RECIST v1.1

7. Cohort 1 and 2: Progression-Free Survival (Time Frame - Up to 60 months):
To evaluate the efficacy of LN-145 in patients with recurrent, metastatic, or persistent cervical carcinoma by assessing progression-free survival (PFS) as assessed by the Investigator per RECIST v1.1

8. Cohort 1 and 2: Overall Survival (Time Frame - Up to 60 months):
To evaluate overall survival (OS) in patients with recurrent, metastatic, or persistent cervical carcinoma

9. Cohort 1 and 2: Adverse Events (Time Frame - Up to 60 months):
To characterize the safety profile of LN-145 in patients with recurrent, metastatic, or persistent cervical carcinoma as assessed by incidence of adverse events

10. Cohort 3: Objective Response Rate (Time Frame - Up to 60 months):
To evaluate the efficacy of LN-145 in combination with pembrolizumab in patients with recurrent, metastatic, or persistent cervical carcinoma based on the objective response rate (ORR) as assessed by the Investigator per RECIST v1.1

11. Cohort 3: Duration of Response (Time Frame - Up to 60 months):
To evaluate the efficacy of LN-145 in combination with pembrolizumab in patients with recurrent, metastatic, or persistent cervical carcinoma by assessing duration of response (DOR) as assessed by the Investigator per RECIST v1.1.

12. Cohort 3: Disease Control Rate (Time Frame - Up to 60 months):
To evaluate the efficacy of LN-145 in combination with pembrolizumab in patients with recurrent, metastatic, or persistent cervical carcinoma by assessing disease control rate (DCR) as assessed by the Investigator per RECIST v1.1.

13. Cohort 3: Progression-Free Survival (Time Frame - Up to 60 months):
To evaluate the efficacy of LN-145 in combination with pembrolizumab in patients with recurrent, metastatic, or persistent cervical carcinoma by assessing progression-free survival (PFS) as assessed by the Investigator per RECIST v1.1.

14. Cohort 3: Overall Survival (Time Frame - Up to 60 months):
To evaluate overall survival (OS) in patients with recurrent, metastatic, or persistent cervical carcinoma

Studien-Arme

  • Experimental: Cohort 1 LN-145 monotherapy
    Post-NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.
  • Experimental: Cohort 2 LN-145 monotherapy
    Patients previously treated with an antiprogrammed cell death protein-1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) checkpoint inhibitor: Post-NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.
  • Experimental: Cohort 3 - Combination Arm (TIL + Pembrolizumab) - US Only
    Patients will be administered with pembrolizumab, followed by NMA lymphodepletion, then infused with their autologous TIL (LN-145) followed by pembrolizumab every 3 or 6 weeks post IL-2 administration up to 24 months.
  • Experimental: Cohort 4 - Non-enrolling Cohort
    Cohort includes patient population not meeting inclusion criteria in cohort 1 and 2. Post-NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.
  • Experimental: Cohort 5 Retreatment Cohort
    Patients who have been previously treated with LN-145 may be given a second treatment with TIL.

Geprüfte Regime

  • 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.
  • LN-145 + pembrolizumab (TIL, autologous tumor infiltrating lymphocytes; pembrolizumab (anti-PD-1 immunotherapy)):
    A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. The first dose of anti-PD-1 immunotherapy will be administered following tumor resection.

Quelle: ClinicalTrials.gov


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