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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
EU CTIS ID: 2024-510634-41-00
What this study is testing
Cohort 1 and 2 – To evaluate the efficacy of LN 145 in patients with recurrent, metastatic, or persistent cervical carcinoma based on the objective response rate as assessed by the Independent Review Committee per Response Evaluation Criteria in Solid Tumors v1.1 Cohort 3 (US only) – To characterize the safety profile of LN-145 in combination with pembrolizumab in patients with recurrent, metastatic, or persistent cervical carcinoma Cohort 4 – To explore the efficacy and safety profile for previously enrolled patients with recurrent, metastatic, or persistent cervical carcinoma treated with LN-145 Cohort 5 – To explore the efficacy and safety profile for re-treated patients with recurrent, metastatic, or persistent cervical carcinoma treated with LN-145 in Cohorts 1 and 2
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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.
You likely can't join if
- 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.
See the full eligibility criteria
Who can join
- 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 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]) 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.
- 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 is permitted as long as the lesions irradiated are not expected to be used for TIL generation or as target lesions and any toxicities have resolved to Grade ≤ 1 at least 2 weeks prior to NMA-LD.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
What rules you out
- 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 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 7 days prior to the start of NMA-LD preparative regimen. Asymptomatic patients with chronic colonization of indwelling urinary diversion tubes may be eligible after active urinary infection is ruled out and discussion with the Medical Monitor. Patients with evidence of any uncontrolled or active systemic infection requiring ongoing treatment cannot proceed to NMA-LD. Prophylactic anti-infection therapy is acceptable.
- 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.
- Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency or acquired immunodeficiency syndrome).
- Patients who have a diagnosis of end-stage renal disorder requiring hemodialysis.
The study team makes the final eligibility decision.
Where it's taking place
- United States
- United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling female, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; United Kingdom. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.