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

Phase 1

Recruiting

• Conditions: Metastatic Non-Small-Cell Lung Cancer; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2024-510778-26-00
• Lead Sponsor: Iovance Biotherapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-28
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

1. Provide written informed consent and written authorization for use and disclosure of protected health information., 10. Have a left ventricular ejection fraction (LVEF) >45% and be New York Heart Association (NYHA) Class 1., 11. Have adequate pulmonary function.If a patient is unable to perform reliable spirometry due to abnormal upper airway anatomy, a 6-minute walk test may be used to assess pulmonary function. Patients must be able to walk a distance at least 80% of predicted for age and sex with no evidence of hypoxia at any point during the test (ie, saturation of peripheral oxygen [SpO2] must remain =90%)., 12. Have completed/discontinued chemotherapy =21 days prior to tumor harvest., 13. Must have recovered from all prior anticancer treatment-related adverse events to Grade=1 (per CTCAE v5.0). Patients with irreversible toxicity (eg, alopecia, vitiligo) after prior anticancer therapies that are not considered by the Investigator to be a likely safety risk may qualify for the study after discussion with the Medical Monitor, 14. Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method ofhighly effective birth control during treatment and for 12 months after receiving all protocol-related therapy., 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 health authority approved 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 demonstratedradiographic 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, 8. Required hematologic parameters: •Absolute neutrophil count =1000/mm3. •Hemoglobin =8.0 g/d

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., 10.Have a history of hypersensitivity to any component of the study drugs. LN-145 should not be administered to patients with a known hypersensitivity to any component of the autologous TIL product formulation, including, but not limited to, any of the following: •NMA-LD (cyclophosphamide, mesna, and fludarabine) •Proleukin®, aldesleukin, IL-2 •Antibiotics of the aminoglycoside group (ie, streptomycin, gentamicin). These patients may be eligible if current hypersensitivity has been excluded. •Any component of the TIL product formulation, including dimethyl sulfoxide (DMSO), human serum albumin (HSA), IL-2, or dextran-40, 11.Have had another primary malignancy within the previous 3 years (except for malignancies that do not require treatment or have been curatively treated >1 year ago, and in the judgment of the Investigator do not pose a significant risk of recurrence including, but not limited to: in situ carcinoma of the cervix; early stage skin cancer, including nonmelanoma skin cancer; ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) of the breast; prostate cancer with Gleason score =6; or superficial bladder cancer)., 12.Participated in another clinical study with an investigational product within 21 days prior to enrollment with the exception of investigational programmed cell death-1 (PD-1)/PD-L1 inhibitors or tyrosine kinase inhibitors (TKIs), which may be continued until 7 days prior to initiation of NMA-LD, 13.Have any condition or characteristic (eg, known psychiatric diagnosis/symptoms, alcohol abuse, or substance abuse) that, in the opinion of the Investigator, could interfere with the evaluation or interpretation of study treatment, patient safety, or study results, 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:, 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 (ßHCG) test with minimum sensitivity of 25 IU/L ß-HCG (or equivalent) at Screening., 6.Are pregnant or breastfeeding. Female patients of childbearing potential must have a negative beta-human chorionic gonadotropin (ßHCG) test with minimum sensitivity of 25 IU/L ß-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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified