A clinical study to investigate if the investigational product, called LN -145 (also known as Tumor Infiltrating Lymphocytes) is safe and beneficial in the treatment of patients with Metastatic Non-Small-Cell Lung Cancer
- Conditions
- Metastatic Non-Small-Cell Lung CancerMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-003629-45-NL
- Lead Sponsor
- Iovance Biotherapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 148
• Provide written informed consent and written authorization for use and disclosure of protected health information.
• Be = 18 years of age at the time of consent.
• Have histologically or pathologically confirmed diagnosis of NSCLC (squamous, nonsquamous, adenocarcinoma, large cell, or mixed histologies), and must have documented PD-L1 expression status, as determined by the tumor proportion score (TPS) prior to the CPI treatment that they received (TPS < 1% for Cohorts 1 and 3, and TPS = 1% for Cohort 2)
• Have received a single line of systemic therapy that included CPI and chemotherapy concurrently, with documented radiographic disease progression on or following this single line of systemic therapy.
• Have documented exercise tolerance no less than 85% of their age-expected normal range and no signs or symptoms of ischemia or clinically significant arrhythmias.
• Have ECOG performance status of 0 or 1 and an estimated life expectancy of > 6 months, in the Investigator’s opinion.
• Cohorts 1 and 2: Have at least one resectable lesion (or aggregate lesions) of a minimum 1.5 cm in diameter for TIL production. Cohort 3 only: Patients must have a single RECIST v1.1-measurable lesion and no additional lesion available for surgical harvest, or be unable to safely undergo a surgical harvest for TIL generation, but able to safely have tumor harvest via radiology guided core biopsy sufficient for TIL generation. Cohort 4: May follow either paradigm. All Cohorts: If the lesion considered for harvest is within a previously irradiated field, the lesion must have demonstrated radiographic progression prior to harvest, and the irradiation must have been completed at least 3 months prior to enrollment.
• Following tumor harvest for TIL manufacturing, all patients must have at least one remaining measurable lesion, as defined by RECIST v1.1, with the following considerations:
a. Lesions in previously irradiated areas should not be selected as target lesions unless progression has been demonstrated in those lesions and the irradiation has been completed at least 3 months prior to enrollment.
b. Cohorts 1 and 2 only: Lesions that are surgically partially resected for TIL generation that are still measurable per RECIST v1.1 may be selected as nontarget lesions but cannot serve as a target lesion for response assessment.
c. Cohort 3 only: If no other lesion is available for core biopsy for TIL generation, the single RECIST v1.1 measurable lesion may serve as both the harvest site for the core biopsies and the lesion for response monitoring.
d. Cohort 4: May follow either paradigm but must have at least 1 RECIST v1.1 measurable lesion to follow for response.
• Have the following hematologic parameters independent of transfusions and/or blood product support for at least 5 days prior to laboratory testing:
a. Absolute neutrophil count (ANC) = 1000/mm3
b. Hemoglobin = 9.0 g/dL
c. Platelet count = 100,000/mm3
• Have adequate organ function with the following laboratory values:
a. Serum alanine aminotransferase and aspartate aminotransferase = 3 times the upper limit of normal (= 3 × ULN); patients with liver metastasis = 5 × ULN
b. Estimated creatinine clearance (eCrCl) = 40 mL/min using the Cockcroft-Gault formula at Screening
c. Total bilirubin = 2 mg/dL; patients with Gilbert’s Syndrome must have a total bilirubin = 3 mg/dL
• Have a left ventricular ejection fraction > 45% and be New York Heart Association (NYHA) Class 1; a cardiac stress test is req
• Have received an organ allograft or prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen within the past 20 years. Patients being retreated with LN-145 are not excluded due to their prior NMA-LD.
• Have known oncogene driver mutations (eg, EGFR, ALK, ROS) which are sensitive to targeted therapies.
• Have symptomatic and/or untreated brain metastases, with the following considerations:
a. Patients with historical (prior to consenting for study participation) definitively treated brain metastases will be considered for enrollment after discussion with Medical Monitor if, prior to enrollment the patient is clinically stable for = 2 weeks, there are no new brain lesions via screening magnetic resonance imaging (MRI), and the patient does not require ongoing corticosteroid treatment.
b. Patients with recently (within 28 days prior to enrollment), definitively treated brain metastases will be considered for enrollment after discussion with Medical Monitor if, prior to enrollment the metastases are asymptomatic, and the patient is clinically stable for = 2 weeks. Prior to initiation of NMA-LD, the following are required: a repeat brain MRI at least 4 weeks posttreatment demonstrating that there are no new or increasing brain lesions, and confirmation that patient is clinically stable for = 2 weeks and does not require ongoing steroid treatment.
• Require systemic steroid therapy > 10 mg/day of prednisone or other steroid equivalent dose. Patients receiving steroids as replacement therapy for adrenocortical insufficiency at = 10 mg/day of prednisone or another steroid equivalent dose are not excluded.
• Have weight loss > 10% since metastatic NSCLC diagnosis.
• Have serologic evidence of any of the following:
a. Human immunodeficiency virus (HIV)-1 or HIV-2
b. Serologic evidence of active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. . Patients with acute or chronic hepatitis infections may be enrolled if the viral load by polymerase chain reaction (PCR) is undetectable with/without active treatment.
c. Syphilis (rapid plasma reagin [RPR] test or venereal disease research laboratory [VDRL]) test)
d. Cytomegalovirus (CMV) immunoglobulin M (IgM) antibody and viral load PCR; and Epstein-Barr virus (EBV) IgM and viral load PCR, indicating active infection
e. Herpes simplex virus (HSV)-1 and HSV-2 IgM serology and viral load PCR.
c. Syphilis (rapid plasma reagin [RPR] test or venereal disease research laboratory [VDRL]) test)
d. Cytomegalovirus (CMV) immunoglobulin M (IgM) antibody and viral load PCR; and Epstein-Barr virus (EBV) IgM and viral load PCR, indicating active infection
e. Herpes simplex virus (HSV)-1 and HSV-2 IgM serology and viral load PCR.
• Be pregnant or breastfeeding.
• Have active medical illness(es) that in the opinion of the Investigator would pose increased risks for study participation, such as systemic infections (eg, syphilis or any other infection requiring antibiotics); coagulation disorders; other active major medical illnesses of the cardiovascular, respiratory, or immune systems; or any history of COVID-19 infection with residual pulmonary compromise.
• Have received a live or attenuated vaccination within 28 days prior to the start of NMA-LD.
• Have any form of primary immunodeficiency (eg, severe combined immunodeficiency disease [SCID] or acquired immune deficiency syndrome [AIDS]).
• Have a history of hypersensitivity to any component of the
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