A Phase II, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144/LN-145/LN-145-S1) in Patients With Solid Tumors.

Study Identifier:
IOV-COM-202
CT.gov Identifier:
NCT03645928
EudraCT Identifier:
201800000000
EU Trial (CTIS) Number:
2024-510779-39-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

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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.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Melanoma
HNSCC
Non-Small Cell Lung Cancer
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase II
Sex
Female & Male
Age
18 - 70 Years
Study Drug
Drug: Patients in Cohorts 1A, 2A, 3A and 3C will receive TIL plus checkpoint inhibitors. Patients in Cohorts 1B, 1C, and 3B will receive autologous TIL as a single therapy.
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Drug: Intervention/treatment
Drug: Drug: Pembrolizumab
Drug: Pembrolizumab will be administered following tumor resection and will continue every 3 weeks or every 6 weeks thereafter for up to 2 years.
Drug: Experimental: Cohort 1B
Drug: Experimental: Cohort 1C
Drug: Ipilimumab will be administered as a single dose prior to tumor resection.
Drug: Nivolumab will be administered once prior to tumor resection. The second dose will be administered prior to TIL administration and dosing will continue every 4 weeks for up to 2 years.
Drug: Experimental: Cohort 1D
Drug: Biological: Lifileucel
Drug: Drug: Nivolumab-relatlimab
Drug: Experimental: Cohort 3D
Drug: Drug: Cisplatin
Drug: Drug: Carboplatin
Drug: Drug: Paclitaxel
Drug: Drug: Nab-Paclitaxel
Drug: Drug: Pemetrexed
Drug: Experimental: Cohort 3E
Drug: Per Annals of Oncology 2018:
Drug: AACR 2021
Drug: Patients received cyclophosphamide and fludarabine is administered preceding a single LN-144 infusion, followed by < 6 doses of IL-2 (600,000 IU/kg). Pembro is administered after tumor harvest but prior to NMA-LD and continues after lifileucel per label.
Drug: WCLC 2021:
Drug: As per EUCTR
Drug: WCLC 2023:
Drug: 2024 ASCO:
Drug: SITC 2024:
Drug: ASCO 2025:
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • 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.
  • EUCT:
  • All patients must have a histologically or pathologically confirmed diagnosis of malignancy: • Unresectable or metastatic melanoma Stage IIIC to IV (Cohorts 1A, 1B, and 1C) • Advanced, recurrent or metastatic HNSCC (Cohort 2A) • Stage III or Stage IV NSCLC (Cohorts 3A, 3B and 3C)
  • 2 Cohorts 1A, 2A, and 3A: If previously treated, patients must have progressed on or after most recent therapy and must not have received CPIs as part of one of the counted lines of prior therapy.
  • 3 Cohorts 1C, 3B, and 3C: Unresectable or metastatic melanoma patients in Cohorts 1C must have previously received systemic therapy with a PD-1 blocking antibody.
  • 4 Patients must have at least 1 resectable lesion (or aggregate lesions) that, in the assessment of the Investigator, has an expected minimum 1.5 cm diameter for TIL production. It is encouraged that tumor tissue be obtained from multiple and diverse metastatic lesions, as long as the surgical resection does not pose additional risks to the patient.
  • 5 Patients must have remaining measurable disease as defined by RECIST 1.1 following tumor resection for TIL manufacturing.
  • 6 Patients must be ≥18 years at the time of consent in all cohorts. Enrollment of patients > 70 years of age may be allowed after consultation with the Medical Monitor.
  • 7 Patients must have an Eastern Cooperative Oncology Group performance status of 0 or 1, and an estimated life expectancy of ≥6 months in the opinion of the Investigator.
  • 8 Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and for 12 months after their last dose of IL-2, 4 months after their last dose of pembrolizumab, or 5 months after their last dose of ipilimumab or nivolumab, whichever occurs later. Additionally, males may not donate sperm and females may not donate eggs during the required contraception period.
  • 9 Patients must have the following hematologic parameters: • Absolute neutrophil count ≥1000/mm³ • Hemoglobin ≥8.0 g/dL • Platelet count ≥100,000/mm³
  • 10 Patients must have adequate organ function: • ALT/SGPT and AST/SGOT ≤3 times the upper limit of normal; patients with liver metastasis ≤5 times ULN • An estimated creatinine clearance ≥40 mL/min at Screening using the Cockcroft-Gault formula • Total bilirubin ≤2 mg/dL • Patients with Gilbert's Syndrome must have a total bilirubin ≤3 mg/dL
  • 11 Patients must have no evidence of any active viral, bacterial, or fungal infection requiring ongoing systemic treatment or as per required screening tests.
  • 12 Patients must have a washout period from prior anticancer therapy(ies) of a minimum duration as defined in the protocol (i.e., start of NMA LD or pembrolizumab or ipilimumab/nivolumab).
  • 13 Patients must have recovered from all prior anticancer TRAEs to Grade ≤1, except for alopecia or vitiligo.
  • 14 Patients with stable Grade ≥ 2 toxicity from prior anticancer therapy may be considered on a case-by-case basis after consultation with the Medical Monitor.
  • 15 Cohort 1A, 2A, 3A and 3C: Patients with stable irreversible toxicity not reasonably expected to be exacerbated by treatment with CPI. For patients in Cohorts 1C, 3B, and 3C (if applicable): documented Grade ≥2 diarrhea or colitis as a result of a previous treatment with CPI(s) must have been asymptomatic for at least 6 months or had a normal by visual assessment colonoscopy post-treatment prior to enrollment.
  • 16 Patients must have provided written authorization for use and disclosure of protected health information.
  • 17 In the opinion of the Investigator, the patient must be able to complete all study required procedures and have the ability to
  • 1 message queued. Will send after the current response.
Exclusion criteria
  • 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 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.
  • EUCT:
  • Patients with melanoma of uveal/ocular origin.
  • 2 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.
  • 3 Patients who have symptomatic untreated brain metastases (with detailed provisions for asymptomatic, historically treated, recently treated, and progressive cases).
  • 4 Patients who are on systemic steroid therapy > 10 mg/day of prednisone or other steroid equivalent.
  • 5 Patients who are pregnant or breastfeeding.
  • 6 Patients who have an active medical illness(es) which would pose increased risks for study participation (e.g., systemic infections, coagulation disorders, or major cardiovascular, respiratory, or immune system illnesses).
  • 7 Cohorts 1A, 2A, 3A, and 3C: Active autoimmune disorders requiring active treatment (with exceptions for vitiligo, alopecia, stable thyroid dysfunction, non-systemic chronic skin conditions, and diet-controlled celiac disease).
  • 8 Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment.
  • 9 Patients who have any form of primary immunodeficiency (such as SCID and AIDS).
  • 10 Patients with a history of hypersensitivity to any component of the study drugs (TIL, NMA-LD, IL-2, aminoglycoside antibiotics, pembrolizumab, ipilimumab, nivolumab).
  • 11 Patients who have LVEF < 45% or who are NYHA Class II or higher.
  • 12 Patients requiring pulmonary function testing (history of ≥ 20 pack-year smoking, ceased smoking within past 2 years, history of COPD, or any signs/symptoms of respiratory dysfunction).
  • 13 Patients who have had another primary malignancy within the previous 3 years (with exceptions for non-melanoma skin cancer, DCIS, LCIS, and prostate cancer Gleason score ≤6).
  • 14 Participation in another interventional clinical study within 21 days prior to the initiation of treatment.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Bernard Doger de Speville
Status
Recruitment Complete
Condition(s) Treated at Site
Melanoma
HNSCC
Non-Small Cell Lung Cancer