A study to investigate the efficacy and safety of the lifileucel (LN-144, autologous tumorinfiltrating lymphocytes [TIL]) regimen plus pembrolizumab infusions compared with pembrolizumab infusions alone in participants with untreated, unresectable or metastatic melanoma
- Conditions
- MelanomaMedDRA version: 21.1Level: LLTClassification code: 10053571Term: Melanoma Class: 10029104Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- CTIS2022-503140-41-00
- Lead Sponsor
- Iovance Biotherapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 670
1. Participant is 18 to 70 years of age at the time of signing the informed consent form, 10. Participant provided written authorization for use and disclosure of protected health information., 11. Participant has the following hematologic parameters: • ANC =1000/mm3 or =1 × 109/L • Hemoglobin =8.0 g/dL or =4.96 mmol/L • Platelet count =100,000/mm3 or =100 × 109/L, 12. Participant has adequate organ function with the following laboratory values: • Serum ALT and AST =3 × ULN; participants with liver metastasis may have ALT and AST =5 × ULN • Total bilirubin =2 mg/dL; participants with Gilbert’s Syndrome may have total bilirubin =3 mg/dL • Estimated CrCl =40 mL/min using the Cockcroft-Gault formula, 13. Participant has an LVEF >45% and is NYHA Class 1. For participants =60 years of age, 14. A participant who meets any of the following criteria must, post-bronchodilator, achieve either a FEV1/FVC >70% or FEV1 >50%: • Has a history of cigarette smoking of =20 pack-years • Ceased smoking within the past 2 years or continues to smoke • Has a history of COPD • Has any signs or symptoms of respiratory dysfunction • Has a history of pleural drainage within the past 3 months, 15. Participant is willing to receive optimal supportive care, including intensive care, from enrollment until the first post treatment tumor assessment., 2. Participant has a histologically or pathologically confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma., 3. In the investigator’s assessment, the participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of > 6 months., 4. Participant is assessed as having at least one resectable lesion (or aggregate lesions) with an estimated minimum diameter of 1.5 cm for lifileucel generation., 5. Participant will have at least one measurable lesion, as defined by RECIST v1.1, at Baseline/cBaseline., 6. If the participant has pre-planned surgical procedure(s), the procedure will take place at least 14 days (for major operative procedures) prior to the tumor resection. Wound healing will have occurred, and all complications will have resolved at the time of tumor resection., 7. Participant has recovered from all prior anticancer treatment-related AEs to Grade =1, 8. The participant agrees to abide by the following: a. Male Participants: Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 12 months after the last dose of study intervention: • Refrain from donating sperm PLUS, either: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent OR - Must agree to use contraception as detailed below: Agree to use a male condom with female partner use of an additional highly effective contraceptive method with a failure rate of <1% per year as described in Appendix 4. These participants should also be advised of the importance for a female partner of childbearing potential who is not currently pregnant to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse b. Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of nonchildbearing potential (WONCBP) as defined in Appendix 4 OR • Is a WOCBP and using a contraceptive method that is highly ef
1. Participant has melanoma of uveal/ocular origin., 10. Participant requires systemic steroid therapy >10 mg/day of prednisone or another steroid equivalent dose., 11. Participant received or will receive a live or attenuated vaccination within 28 days prior to the start of the NMA-LD, 12. Participant has evidence of any active viral, bacterial, or fungal infection requiring ongoing systemic treatment or that is identified during screening, 2. Participant has symptomatic untreated brain metastases. Participants with brain metastases may be evaluated for study participation with the following considerations: • Participants with asymptomatic brain metastases who do not clinically require treatment may be considered for study participation. • A participant with historically treated brain metastases (ie, treatment was completed >28 days prior to consenting for study participation) may be considered for study participation if the participant is clinically stable for =2 weeks, there are no new or worsening brain lesions via screening MRI, and the participant does not require ongoing corticosteroid treatment (>10 mg/day prednisone or equivalent). • If there are progressive or new brain metastases on the screening MRI, the participant should first receive treatment for them prior to restarting or continuing screening. A participant with recently treated brain metastases (ie, treatment of brain metastases was completed =28 days prior to consenting for study participation) may be considered for study participation if the participant is asymptomatic, clinically stable for =2 weeks, and does not require corticosteroids (>10 mg/day prednisone or equivalent) by the end of the screening period. Repeat brain imaging is not required after treatment; however, brain imaging is required at Baseline., 3. Participant received any of the following previous therapies: • Participant received more than 1 prior line of therapy • Participant received prior therapy for metastatic disease • Participants with a BRAF V600 mutation-positive tumor received prior adjuvant/neoadjuvant ICI therapy only, 4. Participant has an active medical illness(es) that, in the opinion of the investigator, would pose increased risks for study participation, such as systemic infections; seizure disorders; coagulation disorders; or other active major medical illnesses of the cardiovascular, respiratory, or immune systems., 5. Participant has active uveitis that requires active treatment. Participants with a history of uveitis must have an eye examination performed by a trained eye specialist at Screening to rule out active uveitis that requires treatment., 6. Participant has any form of primary or acquired immunodeficiency (eg, SCID or AIDS)., 7. Participant has a history of hypersensitivity to any component of the study intervention, 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 participants may be eligible if current hypersensitivity has been excluded. • Any component of the lifileucel product formulation, including DMSO, HSA, IL-2, or dextran 40 • Pembrolizumab, 8. Participant had another primary malignancy within the previous 3 years (except for those that do not require treatment or were curatively treated >1 year ago, and in the judgment of the investigator do not pose a significant risk of recurrence in
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method