A study to find out if an investigational product, called LN-145 (also called tumor infiltrating lymphocytes) is an effective and safe treatment in patients with recurrent, metastatic or persistent cervical carcinoma

Phase 1

Recruiting

• Conditions: Recurrent, metastatic, or persistent Cervical Carcinoma; MedDRA version: 21.1Level: LLTClassification code: 10008229Term: Cervical cancer Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2024-510634-41-00
• Lead Sponsor: Iovance Biotherapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-29
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 189

Inclusion Criteria

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., Must meet the following laboratory criteria: Absolute neutrophil count (ANC) = 1000/mm3; Hemoglobin (Hb) = 8 g/dL or = 4.96 mmol/L; Platelet count = 100,000/mm3 Serum Alanine Transaminase (ALT)/ Serum Glutamic-Pyruvic Transaminase (SGPT) and aspartate Transaminase (AST)/ Serum Glutamic-oxaloacetic transaminase (SGOT) < 3.0 times the upper limit of normal (ULN). Patients with liver metastasis must have Liver Function Tests (LFTs) < 5.0 times the ULN. Total bilirubin = 2.0 mg/dL. Patients with Gilbert's syndrome must have a total bilirubin = 3.0 mg/dL. Serum creatinine must be = 1.5 mg/dL. Measured Creatinine Clearance (CrCl) = 40mL/min calculated from a 24-hour urine collection., 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 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 hepatitis infections may be enrolled if the viral load by polymerase chain reaction (PCR nucleic acid amplification test (NAAT) is undetectable with/without active treatment., Patients of childbearing potential must be willing to take 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., Patients must have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an ICF approved by an Institutional Review Board/Independent Ethics Committee, and agree to abide by the study restrictions and return to the site for the required assessments, including the OS Follow-up Period., Must be able and willing to comply to the study visit schedule and protocol requirements., Must have recurrent, metastatic, or persistent SCC, ASC, or AC of the cervix that is not amenable to curative treatment with surgery and/or radiation therapy and, in Germany and Switzerland only, for which no other therapies are expected to have significant benefit, in the opinion of the Investigator., At least one resectable lesion (or aggregate of leasions 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)., At least one measurable target lesion, as defined by RECIST v1.1: lesions in previously irradiated areas (or other local therapy) should not be selected as target lesions, unless treatment was = 3 months prior to enrollment, and there has been demonstrated disease progression in that particular lesion. If a lesion is partially resected to generate TIL, and remains visible on the Baseline scan after surgery, then the partially resected lesion can be used for RECIST v1.1 response assessment, but only as a non-target lesion., Cohort 1 and 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

Exclusion Criteria

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., Patients who have a left ventricular ejection fraction < 45% or who are New York Heart Association Class 2 or higher. Patients = 60 years of age or who have a history of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias must have a cardiac stress test (or equivalent local standard stress test): Patients with an abnormal cardiac stress test may be enrolled if they have adequate ejection fraction (= 45%) and cardiology clearance after consultation of the Medical Monitor. Patients with any irreversible wall movement abnormalities are excluded., Patients who have a documented forced expiratory volume in 1 second (FEV1) = 60%., 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 judgment of the Investigator, does not pose a significant risk of recurrence including, but not limited to, non-melanoma skin cancer or bladder cancer)., Patients who require systemic steroid therapy (> 10 mg/day of prednisone or other steroid equivalent dose). Patients receiving steroids as replacement therapy for any reason adrenocortical insufficiency at = 10 mg/day of prednisone or other steroid equivalent may be eligible., Patients who currently have prior therapy-related toxicities Grade > 1 according to NCI-Common Terminology Criteria for Adverse Events v5.0 (eg. uveitis); except for peripheral neuropathy, alopecia or vitiligo prior to enrollment (tumor resection). Patients with a history of uveitis must have an eye examination performed by a trained eye specialist at Screening to rule out active uveitis that requires treatment. Patients who have active uveitis that requires active treatment will be excluded. If toxicities have resolved to Grade = 1, a minimum of 2 weeks must elapse 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. Cohort 2: Patients with documented Grade = 2 diarrhea or colitis as a result of previous treatment with a PD-1/PD-L1 checkpoint inhibitor(s) must have been asymptomatic for at least 6 months or had a normal colonoscopy post-checkpoint inhibitor treatment, by visual assessment, prior to tumor resection. Cohort 2: Patients with immunotherapy-related endocrinopathies stable for at least 6 weeks (eg, hypothyroidism, stable on hormonal substitution) and controlled with hormonal replacement, are allowed., No longer applicable, 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); antibiotics (ABX) of the aminoglycoside group (i.e. streptomycin, gentamicin); except those who are skin-test negative for gentamycin hypersensitivity; any component of the LN-145 infusion product formulation., 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 Invest

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified