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

Cervical Carcinoma Clinical Trial

Official title:

A Phase 2, Multicenter Study to Evaluate the Efficacy and Safety Using Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients With Recurrent, Metastatic or Persistent Cervical Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03108495
• Other study ID #: C-145-04
• Secondary ID: 2016-003447-11
• Status: Recruiting
• Phase: Phase 2
• Start date: June 22, 2017
• Est. completion date: December 2030

Study information

• Verified date: February 2024
• Source: Iovance Biotherapeutics, Inc.
• Contact: Iovance Biotherapeutics Clinical Inquiries
• Phone: 650-260-7120
• Email: Clinical.Inquiries[@]iovance.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prospective, multicenter, single-arm, open label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor infiltrating lymphocytes (TIL) infusion (LN-145) followed by IL-2 after a non-myeloablative (NMA) lymphodepletion preparative regimen for the treatment of patients with recurrent, metastatic, or persistent cervical carcinoma

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 189
• Est. completion date: December 2030
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 (SCC), adenosquamous carcinoma (ASC), or adenocarcinoma (AC) 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 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]) in the setting of recurrent, metastatic, or persistent disease either as monotherapy or in combination (eg, in combination with chemotherapy or another immune agent)

Cohort 3 (United States only): 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, including chemotherapy, biologic/targeted agents, and immunologic agents must be discontinued at least 28 days prior to tumor resection.

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

8. Must have adequate organ function.

9. Patient has no evidence of any active viral, bacterial, or fungal infection requiring ongoing systemic treatment. Patients must be seronegative for the human immunodeficiency virus (HIV). Patients with acute or chronic hepatitis infections may be enrolled if the viral load by nucleic acid amplification test (NAAT) is undetectable with/without active treatment

10. 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.

11. Prior to study Enrollment (tumor resection), patient must have documentation of radiological disease progression after the most recent therapy

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for participation in this study:

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 require ongoing systemic steroid therapy (> 10 mg/day of prednisone or other steroid equivalent dose).

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).

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 illness(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 are of the following protected classes will be excluded, including:

• Pregnant, parturient, or breastfeeding women

• Persons who are hospitalized without consent or those deprived of liberty because of a judiciary or administrative decision

• Patients with a legal protection measure or a person who cannot express his/her consent

• Patients in emergency situations who cannot consent to the study

13. Patients who have received a live or attenuated vaccine within 28 days prior to beginning the NMA-LD preparative regimen

14. Patients whose cancer requires immediate attention or who would otherwise suffer a disadvantage by participating in this study

15. 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)

16. Patients who have Grade = 2 hemorrhage within 14 days prior to Enrollment (tumor resection)

17. 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.]).

Related Conditions & MeSH terms

• Carcinoma
• Cervical Carcinoma

Intervention

Biological:
• LN-145
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes.
• LN-145 + pembrolizumab
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.

Locations

Country	Name	City	State
France	Centre Léon Bérard	Lyon
France	Centre Hospitalier Lyon Sud	Pierre Bénite	Rhone-alpes
France	Gustave Roussy Cancer Campus	Villejuif Cedex
Germany	Universitätsklinikum Carl Gustav Carus	Dresden	Sachsen
Germany	Universitätsklinikum Erlangen	Erlangen	Bayern
Italy	Istituto Europeo di Oncologia	Miano	Milano
Netherlands	Academisch Medisch Centrum	Amsterdam	AZ
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Institut Català d'Oncologia	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Madrid Sanchinarro	Madrid
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
Switzerland	Inselspital	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois Lausanne - Centre Pluridisciplinaire d'Oncologie	Lausanne
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow	Scotland
United Kingdom	Guy's & St.Thomas NHS Foundation Trust	London
United Kingdom	Sarah Cannon Research Institute London	London	England
United Kingdom	University College London Hospitals NHS Foundation Trust	London	England
United States	Augusta University	Augusta	Georgia
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Virginia	Charlottesville	Virginia
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Southern California	Los Angeles	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	LSU Health Sciences Center	New Orleans	Louisiana
United States	Rutgers University	Newark	New Jersey
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Florida Health Cancer Center	Orlando	Florida
United States	St. Joseph's Hospital and Medical Center Center For Women's Health	Phoenix	Arizona
United States	Allegheny Health	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center	Pittsburgh	Pennsylvania
United States	University of California San Diego	San Diego	California
United States	Avera Medical Group Oncology	Sioux Falls	South Dakota
United States	University of South Florida H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Iovance Biotherapeutics, Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Netherlands,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort 1 and 2: Objective Response Rate	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	Up to 6 months
Primary	Cohort 3: Adverse Events	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.	Up to 60 months
Primary	Cohort 4: Efficacy and Adverse Events	To explore the efficacy and safety profile of LN-145 in previously enrolled patients with recurrent, metastatic, or persistent cervical carcinoma	Up to 60 months
Primary	Cohort 5: Efficacy and Adverse Events	To explore the efficacy and safety profile of LN-145 in re-treated patients with recurrent, metastatic, or persistent cervical carcinoma	Up to 60 months
Secondary	Cohort 1 and 2: Duration of Response	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	Up to 60 months
Secondary	Cohort 1 and 2: Disease Control Rate	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	Up to 60 months
Secondary	Cohort 1 and 2: Progression-Free Survival	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	Up to 60 months
Secondary	Cohort 1 and 2: Objective Response Rate	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	Up to 60 months
Secondary	Cohort 1 and 2: Duration of Response	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	Up to 60 months
Secondary	Cohort 1 and 2: Disease Control Rate	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	Up to 60 months
Secondary	Cohort 1 and 2: Progression-Free Survival	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	Up to 60 months
Secondary	Cohort 1 and 2: Overall Survival	To evaluate overall survival (OS) in patients with recurrent, metastatic, or persistent cervical carcinoma	Up to 60 months
Secondary	Cohort 1 and 2: Adverse Events	To characterize the safety profile of LN-145 in patients with recurrent, metastatic, or persistent cervical carcinoma as assessed by incidence of adverse events	Up to 60 months
Secondary	Cohort 3: Objective Response Rate	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	Up to 60 months
Secondary	Cohort 3: Duration of Response	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.	Up to 60 months
Secondary	Cohort 3: Disease Control Rate	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.	Up to 60 months
Secondary	Cohort 3: Progression-Free Survival	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.	Up to 60 months
Secondary	Cohort 3: Overall Survival	To evaluate overall survival (OS) in patients with recurrent, metastatic, or persistent cervical carcinoma	Up to 60 months