Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT04614103
• Recruitment Status: Recruiting
• First Posted: November 3, 2020
• Last Update Posted: May 9, 2024
• Sponsor: Iovance Biotherapeutics, Inc.
• Information provided by (Responsible Party): Iovance Biotherapeutics, Inc.

Tracking Information

• First Submitted Date: October 21, 2020
• First Posted Date: November 3, 2020
• Last Update Posted Date: May 9, 2024
• Actual Study Start Date: May 7, 2021
• Estimated Primary Completion Date: December 2030 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 6, 2023)

Objective Response Rate [ Time Frame: Up to 60 months ]

To evaluate the efficacy of LN-145 as determined by objective response rate (ORR) in patients with metastatic NSCLC using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as assessed by central review for Cohorts 1 and 2 and by the investigator for Cohorts 3, 4 and the Retreatment Cohort

Original Primary Outcome Measures (submitted: October 28, 2020)

Objective Response Rate [ Time Frame: Up to 60 months ]

To evaluate the efficacy of LN-145 in patients with metastatic NSCLC without an actionable driver mutation who have disease progression on or following a single line of approved systemic therapy consisting of combined immune checkpoint inhibitor(s) (CPI[s]) + chemotherapy ± bevacizumab, as determined by objective response rate (ORR), using the RECIST v1.1, as assessed by the Independent Review Committee (IRC) (Cohorts 1 and 2) or by the Investigator (Cohorts 3 and 4)

Current Secondary Outcome Measures (submitted: June 13, 2022)

• Objective Response Rate [ Time Frame: Up to 60 months ]
  To evaluate the efficacy of LN-145 as determined by objective response rate (ORR) per RECIST v1.1, as assessed by the Investigator for Cohorts 1 and 2
• Complete Response Rate [ Time Frame: Up to 60 months ]
  To evaluate efficacy parameters such as Complete Response Rate (CRR) per RECIST v1.1
• Duration of Response [ Time Frame: Up to 60 months ]
  To evaluate efficacy parameters such as Duration of Response (DOR) rate per RECIST v1.1
• Disease Control Rate [ Time Frame: Up to 60 months ]
  To evaluate efficacy parameters such as Disease Control Rate (DCR) per RECIST v1.1
• Progression-Free Survival [ Time Frame: Up to 60 months ]
  To evaluate efficacy parameters such as Progression-Free Survival (PFS) per RECIST v1.1
• Overall Survival [ Time Frame: Up to 60 months ]
  To evaluate efficacy parameters such as Overall Survival (OS)
• Adverse Events [ Time Frame: Up to 60 months ]
  To characterize the safety profile of LN-145 in patients with non-small-cell lung cancer (NSCLC)
• Core Biopsies [ Time Frame: Up to 60 months ]
  To determine the feasibility of generating LN-145 using tumor tissue obtained via image-guided core biopsy

Original Secondary Outcome Measures (submitted: October 28, 2020)

• Objective Response Rate [ Time Frame: Up to 60 months ]
  To evaluate efficacy parameters such as Objective Response Rate (ORR) per RECIST v1.1
• Complete Response Rate [ Time Frame: Up to 60 months ]
  To evaluate efficacy parameters such as Complete Response Rate (CRR) per RECIST v1.1
• Duration of Response [ Time Frame: Up to 60 months ]
  To evaluate efficacy parameters such as Duration of Response (DOR) rate per RECIST v1.1
• Disease Control Rate [ Time Frame: Up to 60 months ]
  To evaluate efficacy parameters such as Disease Control Rate (DCR) per RECIST v1.1
• Progression-Free Survival [ Time Frame: Up to 60 months ]
  To evaluate efficacy parameters such as Progression-Free Survival (PFS) per RECIST v1.1
• Overall Survival [ Time Frame: Up to 60 months ]
  To evaluate efficacy parameters such as Overall Survival (OS)
• Adverse Events [ Time Frame: Up to 60 months ]
  To characterize the safety profile of LN-145 in NSCLC patients, as measured by the incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs)
• Core Biopsies [ Time Frame: Up to 60 months ]
  For Cohort 3 only: To evaluate the efficiency of generating LN-145 from tumor core biopsies; Percentage successful TIL products generated from core biopsies

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer
• Official Title: A Phase 2 Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (TIL or LN-145) in Patients With Metastatic Non-Small-Cell Lung Cancer
• Brief Summary: This is a prospective, open-label, multi-cohort, non-randomized, multicenter phase 2 study evaluating LN-145 in patients with metastatic non-small-cell lung cancer
• Detailed Description: LN-145 is a ready-to-infuse TIL therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI and further optimized by Iovance for the treatment of patients with metastatic NSCLC. The cell transfer therapy used in this study involves patients receiving a non-myeloablative (NMA) lymphodepleting preparative regimen, followed by infusion of autologous TIL, then finally followed by the administration of IL-2.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Non Small Cell Lung Cancer

Intervention

• Biological: LN-145
  A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145), followed by IL-2.
  Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes
• Biological: LN-145
  A tumor sample is obtained by image-guided core biopsy from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145) followed by IL-2.
  Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes

Study Arms

• Experimental: Cohort 1
  Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1), i.e., tumor proportion score (TPS) < 1% prior to ICI treatment and Patients with no available historical TPS for PD-L1 expression
  Intervention: Biological: LN-145
• Experimental: Cohort 2
  Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment
  Intervention: Biological: LN-145
• Experimental: Cohort 3
  Patients, regardless of tumor PD-L1 TPS prior to ICI treatment, who are unable to safely undergo a surgical tumor resection for TIL generation
  Intervention: Biological: LN-145
• Experimental: Cohort 4
  Patients, regardless of tumor PD-L1 expression status prior to ICI treatment, who have meet all inclusion/exclusion criteria except the requirement to have documented disease progression may elect to have the tumor harvest procedure and TIL production prior to disease progression on their current anticancer treatment. Documentation of progressive disease and identification of a target lesion for RECIST v1.1 assessment is required at Baseline for these patients.
  Intervention: Biological: LN-145
• Experimental: Retreatment Cohort
  Patients who were previously treated with LN-145 in Cohort 1, 2, 3, or 4.
  Intervention: Biological: LN-145

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 6, 2023): 170
• Original Estimated Enrollment (submitted: October 28, 2020): 95
• Estimated Study Completion Date: December 2031
• Estimated Primary Completion Date: December 2030 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients who are over 70 years of age may be allowed to enroll after discussion with the Medical Monitor.
• Have historically or pathologically confirmed diagnosis of metastatic Stage IV NSCLC without EGFR, ALK, or ROS1 genomic alterations.
• For patients who have actionable mutations (other than EGFR, ALK, or ROS1 genomic alterations), 1 additional line of therapy with the appropriate health authority approved targeted therapy is required.
• Patients must have documented radiographic disease progression on or after the first-line therapy, including concurrent or sequential ICI and platinum-based chemotherapy ± bevacizumab. No more than 1 prior line is allowed if ICI and platinum-based chemotherapy were administered concurrently and no more than 2 prior lines are allowed for sequential administration of platinum-based chemotherapy and ICI as 2 separate lines.
• LN-145 manufacture is allowed for patients who have residual resectable disease after completion of the platinum-based chemotherapy component of the front-line ICI and platinum-based chemotherapy combination and meet all eligibility criteria except documented disease progression. These patients must intend to receive TIL therapy after disease progression
• Prior systemic therapy in the adjuvant or neoadjuvant setting, or as part of definitive chemoradiotherapy, will count as a line of therapy if the patient had disease progression during or within 12 months after the completion of such therapy.
• At least 1 resectable lesion for TIL production and at least one remaining measurable lesion, as defined by RECIST v1.1
• Have adequate organ function
• LVEF > 45%, NYHA Class 1
• Have adequate pulmonary function
• ECOG performance status of 0 or 1
• 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 up to 12 months after all protocol-related therapy

Exclusion Criteria:

• Patients who have EGFR, ALK or ROS1 driver mutations
• Patients who have symptomatic, untreated brain metastases.
• Patients who have had allogeneic organ transplant or prior cell therapy within the past 20 years
• Patients who have any form of primary immunodeficiency
• Patients who are on systemic steroid therapy ≥ 10 mg/day of prednisone or equivalent.
• Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment
• Patients who have had another primary malignancy within the previous 3 years
• Participation in another interventional clinical study within 21 days

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Iovance Biotherapeutics Study Team lungcelltherapy.com; 1-844-845-4682; Clinical.Inquiries@iovance.com

• Listed Location Countries: Canada, Germany, Netherlands, Switzerland, United States

Administrative Information

• NCT Number: NCT04614103
• Other Study ID Numbers: IOV-LUN-202; 2020-003629-45 ( EudraCT Number ); 2024-510778-26-00 ( EU Trial (CTIS) Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Iovance Biotherapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Iovance Biotherapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Iovance Biotherapeutics Study Team; Iovance Biotherapeutics

• PRS Account: Iovance Biotherapeutics, Inc.
• Verification Date: May 2024