A Phase II, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144/LN-145/LN-145-S1) in Patients With Solid Tumors.
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Study Summary
To evaluate adoptive cell therapy (ACT) with TIL LN-144 (Lifileucel)/LN-145 in combination with checkpoint inhibitors or TIL LN-144 (Lifileucel)/LN-145/LN-145-S1 as a single agent therapy.
To improve on the efficacy response for early line patients by combining TIL with anti-PD1 in metastatic melanoma and head and neck cancers (Cohorts 1 and 2)
To evaluate the efficacy of autologous TIL LN-144/LN-145 as a single-therapy in NSCLC patients or in combination with pembrolizumab in MM and HNSCC patients by determining the ORR, using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by Investigator.
To characterize the safety profile of TIL LN-144/LN-145 as a single-therapy in NSCLC patients or in combination with pembrolizumab in MM and HNSCC patients as measured by the incidence of Grade =3 treatment-emergent adverse events (TEAEs)
To evaluate:
Whether LN-144/LN-145 alone or in combination with pembrolizumab is safe.
Whether LN-144/LN-145 in combination with pembrolizumab reduces or slows the progression of metastatic melanoma and HNSCC.
Whether LN-144/LN-145 in combination with pembrolizumab eliminates all detectable metastatic melanoma and HNSCC.
Whether LN-145 reduces or slows the progression of NSCLC.
Whether LN-145 eliminates all detectable NSCLC.
Whether treatment with LN-144/LN-145 alone or in combination with pembrolizumab extends the life of a patient without their cancer worsening.
To explore a combination of LN-144 and pembro in patients with ICI-naive advanced melanoma
To report the first safety and efficacy data for LN-145 as monotherapy in patients with advanced NSCLC
To report the first efficacy and safety data for LN-145 autologous TIL cell therapy in combination with pembrolizumab in patients with ICI-naïve metastatic NSCLC.
To evaluates lifileucel combined with anti-PD-1 therapy in front-line advanced melanoma.
Cohort 1A:
To assess the efficacy and safety of lifileucel and pembrolizumab (pembro) in pts with ICI-naive unresectable or metastatic melanoma
Endpoints include ORR, complete response rate, disease control rate, and PFS by investigator-assessed RECIST v.1.1, OS, percentage of manufactured lifileucel drug products that meets release specification, and incidence of grade ≥3 treatment-emergent adverse events.
- Must have a confirmed diagnosis of malignancy of their receptive histologies: unresectable or metastatic melanoma Stage IIIC to IV (Cohorts 1A,1B and 1C), advanced, recurrent or metastatic HNSCC (Cohort 2A), or Stage III or Stage IV non-small cell lung cancer (Cohorts 3A, 3B, and 3C). Stage IV NSCLC with no actionable mutations (EGFR, ALK, ROS1) with effective targeted therapy (Cohorts 3D and 3E).
- Cohorts 1A, 1D, 2A, 3A, 3D and 3E: If previously treated, patients must have progressed on or after most recent therapy and must not have received ICIs as part of one of the counted lines of prior therapy. Patients must have radiologically documented disease progression while receiving or after the completion of the most recent prior treatment. Patients may have received up to 3 prior systemic anticancer therapies (except for Cohort 3A, where patients whose tumors harbor actionable mutations may have received up to 4 prior systemic therapies). Patients in Cohort 1D may have had no prior therapy for advanced disease. Patients in Cohorts 3D and 3E may have had no prior systemic therapy for Stage IV disease.
- Cohorts 1B, 1C, 3B, and 3C: Unresectable or metastatic melanoma patients in Cohorts 1B or 1C must have previously received systemic therapy with a PD-1 blocking antibody. NSCLC patients in Cohort 3B must have previously received systemic therapy with any ICI (except for those patients with known oncogene driver mutations that are sensitive to targeted therapies) as part of 1 - 3 prior lines of therapy. NSCLC patients in Cohort 3C must have previously received 1 line of ICI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neoadjuvant settings are allowed.
- Must have at least 1 resectable lesion
- Must have remaining measurable disease as defined by RECIST 1.1 following tumor resection
- Must be ≥ 18 years at the time of consent for Cohorts 1A, 1C, 1D, 2A, 3A, 3B, 3C, 3D and 3E. Patients must be ≥ 12 years at the time of consent for Cohort 1B. Enrollment of patients > 70 years of age may be allowed after consultation with the Medical Monitor.
- Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and an estimated life expectancy of > or = 6 months.
- Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of birth control during treatment and for 12 months after their last dose of aldesleukin, 4 months after their last dose of pembrolizumab, 5 months after their last dose of ipilimumab or nivolumab, or nivolumab-relatlimab; 6 months after the last dose of carboplatin; 14 months after the last dose of cisplatin; and 6 months after the last dose of pemetrexed, paclitaxel, or nab-paclitaxel, whichever occurs later.
- One resectable lesion for lifileucel manufacturing, and > or = 1 measurable lesion for response assessment.
- Cohort 3A eligibility requires ICI-naïve advanced or metastatic NSCLC with disease progression, ≥1 resectable lesion for LN-145 manufacturing, and ≥1 remaining RECIST v1.1-evaluable lesion.
- Patients with melanoma of uveal/ocular origin.
- Patients who have a history of allogeneic organ transplant or any form of cell therapy involving prior conditioning chemotherapy within the past 20 years. Patients being retreated with TIL, as part of this study are not excluded.
- Patients who have symptomatic, untreated brain metastases or history of leptomeningeal metastases.
- Patients who are on systemic steroid therapy > 10 mg/day of prednisone or other steroid equivalent. Patients receiving steroids as replacement therapy for adrenocortical insufficiency at
- Patients who are pregnant or breastfeeding.
- Patients who have an active medical illness(es), which in the opinion of the Investigator, would pose increased risks for study participation
- Cohort 1A, 1D, 2A, 3A, 3C, 3D and 3E patients may not have a medical history of autoimmune disorders (including pneumonitis) requiring treatment or active management.
- Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment
- Patients who have any form of primary immunodeficiency
- Patients with a history of hypersensitivity to any component of the study drugs to be administered in the pertinent cohort(s).
- Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association Class II or higher. A cardiac stress test demonstrating any irreversible wall movement abnormality in any patients ≥60 years of age or in patients who have a history of ischemic heart disease, cardiac chest pain, or clinically significant atrial and/or ventricular arrhythmias.
- Patients with respiratory dysfunction or history of smoking are excluded if not meeting either of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 0.7 or FEV1 > 50%.
- Patients who have had another primary malignancy within the previous 3 years
- Participation in another interventional clinical study within 21 daysprior tothe initiation of treatment.
- Patients in Cohorts 1D, 3D, or 3E who previously received adjuvant or neoadjuvant ICI(s) for non-metastatic disease and had an immune-related AE(s) requiring systemic steroid treatment or discontinuation of immune checkpoint inhibitor therapy.
Clinical Study Information for Healthcare Providers
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