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
- Conditions
- Recurrent, metastatic, or persistent Cervical CarcinomaMedDRA version: 21.1Level: LLTClassification code 10008229Term: Cervical cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003447-11-DE
- Lead Sponsor
- Iovance Biotherapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 138
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. Patients (or legally authorized representative) 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
3. Must be able and willing to comply to the study visit schedule and protocol requirements.
4. 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 for which no other therapies are expected to have significant benefit, in the opinion of the Investigator.
5. 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).
6. 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.
7. 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 was administered for recurrent, or 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 (United States only): Must have not received any therapies other than prior chemoradiation or surgery for loco-regional disease
8. 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. 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. 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.
9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
10. Must meet the following laboratory criteria: Absolute neutrophil count (ANC) = 1000/mm3; Hemoglobin (Hb) = 8 g/dL or = 5.6 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
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 for any reason.
3. Patients who currently have prior therapy-related toxicities Grade > 1 according to NCI-Common Terminology Criteria for Adverse Events v5.0; except for peripheral neuropathy, alopecia or vitiligo prior to enrollment. If toxicities have resolved to Grade = 1, a minimum of 4 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.
4. No longer applicable
5. 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 including DMSO, HSA, IL-2, and dextran-40
6. 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.
Patients with corrected (ie, percutaneous nephrostomy tubes) urinary tract obstruction must have negative surveillance cultures from externalized tubes within 14 days prior to the start of NMA-LD preparative regimen.
Patients with an intercurrent infection following tumor resection must be infection-free and off ABX for at least 14 days prior to the initiation of NMA-LD preparative regimen.
7. Patients with symptomatic and/or untreated brain metastases. 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.
8. Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency or acquired immunodeficiency syndrome).
9. Patients who have a diagnosis of end-stage renal disorder requiring hemodialysis.
10. 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 in patients who have a history of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias must have a cardiac stress test: Patients with an abnormal cardiac stress test may be enrolled if they have adequate ejection fraction and cardiology clearance with approval of the medical monitor. Patients with any irreversible wall movement abnormalities are excl
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method