Lung Cancer Non-Small-Cell Lung Cancer
Conditions
Interventions
Patients will undergo a 5-day preconditioning NMA-LD regimen that will be
initiated prior to the planned LN-145 infusion on Day 0 (i.e., Days -5 through
1. The NMA-LD regimen consists of 2 days of i
Sponsors
Iovance Biotherapeutics, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent and written authorization for use and disclosure of protected health information. 2. Be 18 to 70 years of age at the time of signing of informed consent form. Patients who are >70 years of age may be allowed to enroll after consultation with the Medical Monitor. 3. Have histologically or pathologically confirmed diagnosis of metastatic Stage IV NSCLC (squamous, nonsquamous, adenocarcinoma, large cell, or mixed histologies) without EGFR, ALK, or ROS genomic alterations. 4. Meet prior therapy criteria: -post-progression tumor harvest: Patient must have documented radiographic disease progression on or after the first-line therapy, inclusive of prior ICI and platinum-based chemotherapy ± bevacizumab or targeted therapy. -pre-progression tumor harvest and TIL production: Patient must have residual resectable disease after completion of the platinum-based chemotherapy component of either concurrent or sequential ICI and platinum-based chemotherapy, meet all eligibility criteria except documented disease progression, and intend to receive TIL therapy after disease progression on current therapy. 5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of >6 months, in the Investigator*s opinion. 6. Cohorts 1, 2 and 4: Have at least 1 resectable lesion (or aggregate lesions) with an expected minimum 1.5 cm diameter for TIL production. Cohort 3: Have a single, measurable lesion (RECIST v1.1) and/or are unable to undergo a surgical tumor resection, but able to undergo tumor harvest for TIL generation via image-guided core biopsy. Retreatment Cohort: Meet any tumor requirement listed above. 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. Patients must have an adequate histopathology specimen for protocol-required testing 7. Have at least 1 remaining measurable lesion as defined by RECIST v1.1 following tumor harvest for TIL manufacturing that is documented at Screening for post disease progression tumor harvest and at Baseline forpre- and post-progression tumor harvest 8.Required hematologic parameters: •Absolute neutrophil count >=1000/mm3. •Hemoglobin >=8.0 g/dL. •Platelet count >=100,000/mm3 9. Have adequate organ function with the following laboratory test values: •ALT and AST =40 mL/min using the Cockcroft-Gault formula at Screening 10. Have a left ventricular ejection fraction (LVEF) >45% and be New York Heart Association (NYHA) Class 1. A cardiac stress test is required for patients over >=60 years of age or who have a history of ischemic heart disease, cardiac chest pain, or clinically significant atrial and/or ventricular arrhythmias; the cardiac stress test must demonstrate no irreversible wall movement abnormality. Patients with an abnormal cardiac stress test may be enrolled if they have adequate ejection fraction and cardiology clearance after discussion with
Exclusion criteria
Exclusion criteria: 1. Have a history of allogeneic organ transplant or any form of cell therapy involving a prior nonmyeloablative or myeloablative chemotherapy regimen within the past 20 years. Patients being retreated with LN-145 are not excluded due to prior NMA-LD during this study. 2. Have known actionable EGFR, ALK, or ROS driver mutations. 3. Have symptomatic untreated brain metastasis. Patients with brain metastases may be enrolled with the following considerations and only after discussion with the Medical Monitor: a.Patients with asymptomatic brain metastases who do not clinically require treatment may be enrolled. b.Patients with historically treated brain metastases (i.e., treatment of brain metastases was completed >28 days prior to date of informed consent) will be considered for enrollment if the patient is clinically stable for >=2 weeks, there are no new or worsening brain lesions via screening magnetic resonance imaging (MRI), and the patient does not require ongoing corticosteroid treatment (>10 mg/day prednisone or equivalent). c.Patients with recently treated brain metastases (i.e., treatment of brain metastases was completed =2 weeks, and does not require corticosteroids (>10 mg/day prednisone or equivalent) d.Patients with progressive or new brain metastases on screening magnetic resonance imaging (MRI) should suspend screening procedures and receive appropriate treatment of brain metastases. Screening can resume after completion of brain metastases treatment, when the patient is asymptomatic, clinically stable for >=2 weeks, and does not require corticosteroids (>10 mg/day prednisone or equivalent) at the start of NMA-LD (Day -5). Note: Patients who develop symptomatic brain metastases at any time after signing the ICF until starting NMA-LD should receive appropriate treatment of brain metastases prior to NMA-LD. Such patients must be asymptomatic, clinically stable for >=2 weeks, and not require corticosteroids (>10 mg/day prednisone or equivalent) at the start of NMA-LD (Day -5) 4. Require systemic steroid therapy >10 mg/day prednisone or equivalent. Patients receiving steroids as replacement therapy for adrenocortical insufficiency at <=10 mg/day prednisone or equivalent are not excluded. 5. Have evidence of any active viral, bacterial, or fungal infection requiring ongoing systemic treatment or as per required screening tests. 6. Are pregnant or breastfeeding. Female patients of childbearing potential must have a negative beta-human chorionic gonadotropin (β-HCG) test with minimum sensitivity of 25 IU/L β-HCG (or equivalent) at Screening. 7. Have an active medical illness(es) that in the opinion of the Investigator would pose increased risks for study participation, such as systemic infections, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune systems. 8. Have received a live or attenuated vaccination within 28 days prior to the start of NMA-LD. 9. Have any form of primary immunodeficiency (eg, severe combined immunodeficiency disease [SCID] or acquired immune deficiency syndrome [AIDS]). 10. Have a history of hypersensitivity to any component of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR is defined as the proportion of patients who have a confirmed CR or PR as assessed per RECIST v1.1 by the IRC (Cohorts 1 and 2) or by the Investigator (Cohort 3, 4 and Retreatment Cohort) from the date of LN-145infusion until disease progression or start of a new anticancer therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: • ORR is defined as the proportion of patients who have a confirmed CR or PR as assessed per RECIST v1.1 by the Investigator (Cohort 1 and 2) from the date of LN-145 infusion until disease progression or start of a new anticancer therapy. •CR rate is defined as the proportion of patients who have a confirmed CR per RECIST v1.1 as assessed by the IRC (Cohort 1 and 2) or by the Investigator (all cohorts) from the date of LN-145 infusion until disease progression or start of a new anticancer therapy. •DOR is measured from the time that criteria are met for CR or PR per RECIST v1.1 as assessed by IRC (Cohorts 1 and 2) or by the Investigator (all cohorts) until disease progression or death due to any cause. •DCR is measured by the percentage of patients with a best overall confirmed response of CR or PR at any time plus stable disease (SD) >= 6 weeks per RECIST v1.1 as assessed by IRC (Cohorts 1 and 2) or by the Investigator (all cohorts) from the date of LN-145 infusion until disease progression or the start of a new anticancer therapy. •PFS is defined as the time from the date of LN-145 infusion until disease progression, per RECIST v1.1 as assessed by IRC (Cohorts 1 and 2) or by the Investigator (all cohorts) or death due to any cause. •OS is the time from the date of LN-145 infusion to death due to any cause. •Incidence of Grade >=3 TEAEs and SAEs per CTCAE v5.0 in all patients•Percentage of successful LN-145 product generated from core biopsies in Cohort 3 Exploratory Endpoints: • In vivo persistence of the T cells comprising the TIL product to be assessed by monitoring the presence of TIL product-specific T-cell receptor-beta complementarity determining region 3 (CDR3) sequences in each patient's blood over time; CDR3 sequences present in the product and peripheral blood samples to be identified using deep sequencing • Exploratory endpoints aiming at identifying predictive and pharmacodynamic clinical biomarkers of | — |
Countries
Netherlands
Outcome results
None listed