2025-522054-40-00招募中2 期
A Phase 2, multicenter, open-label study of lifileucel (tumor-infiltrating lymphocytes [TIL]) in participants with previously treated advanced melanoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 69
- 试验地点
- 18
- 主要终点
- ORR is defined as the proportion of participants who have a confirmed CR or PR per RECIST v1.1 (timeframe: from the date of the lifileucel infusion until disease progression, start of a new anticancer therapy, or death due to any cause, whichever occurs first [up to a maximum of 5 calendar years after the lifileucel infusion]).
研究概览
简要总结
To evaluate the efficacy of lifileucel as measured by ORR per RECIST v1.1 as assessed by the IRC in participants who previously received an anti-PD-(L)1 agent for advanced melanoma and/or prior to early relapse and whose melanoma is either BRAF V600 mutation positive and previously treated with a BRAF inhibitor (± a MEK inhibitor) or is BRAF V600 wild-type (ie, the primary population).
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Follow-Up Period
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Participant must be ≥ 18 years of age at the time of signing the informed consent. Enrollment of participants > 70 years of age may be allowed after discussion with the medical monitor and with consideration of factors including but not limited to performance status, life expectancy, and frailty of the participant.
- •Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male Participants: Participants are eligible to participate if they agree to the following: • Refrain from donating sperm PLUS, either: − Be abstinent from intercourse where pregnancy can occur (abstinent on a long-term and persistent basis) and agree to remain abstinent OR − Must agree to use contraception as detailed below: Agree to use an external condom with CBP partner use of an additional highly effective contraceptive method with a failure rate of < 1% per year. b. Female Participants: A participant is eligible to participate if not pregnant or breastfeeding, and one of the following conditions applies: • Is of nonchildbearing potential (NCBP) OR • Is of CBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), preferably with low user dependency and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention. • A CBP participant must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the tumor resection. • Additional requirements for pregnancy testing during and after study intervention are located in the protocol • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a participant with an early undetected pregnancy.
- •Participant is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- •Participant provided written authorization for use and disclosure of protected health information.
- •Participant has the following hematologic parameters: • Absolute neutrophil count (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
- •Participant has adequate organ function with the following laboratory values: • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN); participants with liver metastasis may have ALT and AST up to 5 × ULN • Total bilirubin ≤ 2 mg/dL; participants with Gilbert’s syndrome may have total bilirubin up to 3 mg/dL • CrCl of ≥ 40 mL/min, measured by 24-hour urine collection (or another clinically validated test as per local practice) or calculated using the Cockcroft-Gault equation. Measured CrCl is required for participants ≥ 65 years of age OR who have urinary tract obstruction.
- •Participant has a left ventricular ejection fraction (LVEF) > 45% and is New York Heart Association (NYHA) Class
- •For participants ≥ 60 years of age OR who have a history of clinically relevant cardiac disease, no clinically significant wall movement abnormality is demonstrated on a cardiac stress test (or equivalent local standard stress test). Participants with an abnormal cardiac stress test may be considered for study participation if they have adequate ejection fraction and cardiology clearance with approval of the medical monitor.
- •A participant who meets any of the following criteria must, with or without a bronchodilator, achieve either a forced expiratory volume in 1 second (FEV1)/forced vital capacity (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 chronic obstructive pulmonary disease (COPD) • Has any signs or symptoms of respiratory dysfunction • Has a history of pleural drainage within the past 3 months. If the participant is unable to perform reliable spirometry due to abnormal upper airway anatomy (ie, tracheostomy), a 6-minute walk test may be used to assess pulmonary function. A participant who is able to walk a distance of at least 80% predicted for age and sex and does not demonstrate evidence of hypoxia at any point during the test (oxygen saturation of peripheral blood [SpO2] < 90%) is eligible for study participation.
- •Participant is willing to receive optimal supportive care, including intensive care, from enrollment until the first post-treatment tumor assessment.
- •The participant has a histologically or pathologically confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma.
- •The participant must have experienced radiographic disease progression on: • 1 prior line of an anti-PD-(L)1 treatment (as a monotherapy or as part of a combination) for advanced melanoma and/or • during or within ≤ 12 weeks after adjuvant anti-PD-(L)1 treatment (as a monotherapy or as part of a combination). Participants who have BRAF V600 mutation positive melanoma may have received 1 additional prior line of treatment with a BRAF inhibitor ± a MEK inhibitor.
- •The participant has an ECOG performance status of 0 or 1 and an estimated life expectancy of > 6 months.
- •Participant is assessed as having at least one resectable lesion (or aggregate lesions) with an estimated minimum diameter of 1.5 cm (short axis) for lifileucel generation. It is preferred that the tumor targeted for resection has not been previously irradiated. If it has, the irradiation must have occurred at least 3 months prior to tumor resection and the irradiated lesion(s) must have unequivocal radiographically demonstrated progression after radiation therapy (RT)
- •Following tumor resection for lifileucel generation, the participant will have at least one measurable lesion, as defined by RECIST v1.1 at Baseline. • Lesions in previously irradiated areas (or areas treated with local therapy) should not be selected as target lesions unless subsequent progression has been demonstrated in those lesions and the irradiation/local therapy was completed at least 3 months prior to the tumor resection for lifileucel generation. • Lesions that are partially resected for lifileucel generation and are still measurable per RECIST v1.1 may be selected as nontarget lesions but cannot serve as a target lesion for the tumor response assessment.
- •Participant is expected to achieve washout from investigational or anticancer therapy(ies).
- •If the participant has preplanned surgical procedure(s), the procedure will take place (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.
- •Participant has recovered from all prior anticancer treatment-related AEs to Grade ≤ 1 (per NCI-CTCAE), except for peripheral neuropathy, alopecia, or vitiligo. Participants with stable Grade 2 toxicity from prior anticancer therapy must have been discussed with the medical monitor. Participants with stable immunotherapy-related endocrinopathies (eg, hypothyroidism) and controlled with hormonal replacement are allowed. Participants with documented Grade ≥ 2 diarrhea or colitis as a result of previous treatment with anti-PD-(L)1 therapy must have been asymptomatic for at least 6 months or had a normal colonoscopy after checkpoint inhibitor treatment, by visual assessment, prior to tumor resection.
排除标准
- •Participants with uveal/ocular melanoma or melanoma with known GNAQ or GNA11 mutation.
- •Participant received or will receive a live or attenuated vaccination within 28 days prior to the start of the NMA-LD preparative regimen.
- •Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
- •Participants with symptomatic untreated brain metastasis. Participants with brain metastases may be enrolled with the following considerations and only after discussion with the medical monitor: • Participants with progressive or new brain metastases on screening MRI should suspend screening procedures and receive appropriate treatment of brain metastases. Screening can resume after completion of brain metastases treatment, when the participant is asymptomatic, clinically stable, and does not require corticosteroids (>10 mg/day prednisone or equivalent). • Participants with historically treated brain metastases will be considered for enrollment if the participant is clinically stable, there are no new or worsening brain lesions via screening MRI, and the participant does not require ongoing corticosteroid treatment (>10mg/day prednisone or equivalent). • Participants with recently treated brain metastases may be considered for enrollment if the participant is asymptomatic, clinically stable, and does not require corticosteroids (>10 mg/day prednisone or equivalent). • Participants with previously known asymptomatic brain metastases who do not clinically require treatment may be enrolled. Note: Participants who develop symptomatic brain metastases at any time after signing the ICF until starting NMA-LD should receive appropriate treatment of brain metastases prior to NMA-LD
- •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; coagulation disorders; or other active major medical illnesses of the cardiovascular, respiratory, or immune systems. Participant has evidence of any active viral, bacterial, or fungal infection requiring ongoing systemic treatment or identified during screening
- •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.
- •Participant has any form of primary immunodeficiency (eg, severe combined immunodeficiency disease [SCID] or AIDS).
- •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 used in lifileucel manufacturing and potentially present in the formulated product (see Section 6.3 of the IB). These participants may be eligible if current hypersensitivity has been excluded. • Any component of the lifileucel product formulation.
- •Participant had another primary malignancy within the previous 3 years (except for those that do not require treatment or have been curatively treated > 1 year ago, and in the judgment of the investigator does not pose a significant risk of recurrence including, but not limited to: in situ carcinoma of the cervix, early stage skin cancer, including non-melanoma 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).
- •Participant has a history of allogeneic organ transplant or any form of cell therapy involving prior conditioning chemotherapy within the past 20 years. Participants being retreated with lifileucel are not excluded due to prior NMA-LD on this study.
- •Participant requires systemic steroid therapy > 10 mg/day of prednisone or another steroid equivalent dose. Participants receiving steroids as replacement therapy for adrenocortical insufficiency at ≤ 10 mg/day of prednisone or another steroid equivalent dose may be eligible.
结局指标
主要结局
ORR is defined as the proportion of participants who have a confirmed CR or PR per RECIST v1.1 (timeframe: from the date of the lifileucel infusion until disease progression, start of a new anticancer therapy, or death due to any cause, whichever occurs first [up to a maximum of 5 calendar years after the lifileucel infusion]).
ORR is defined as the proportion of participants who have a confirmed CR or PR per RECIST v1.1 (timeframe: from the date of the lifileucel infusion until disease progression, start of a new anticancer therapy, or death due to any cause, whichever occurs first [up to a maximum of 5 calendar years after the lifileucel infusion]).
次要结局
- 1. ORR is defined as the proportion of participants who have a confirmed CR or PR per RECIST v1.1 (timeframe: from the date of the lifileucel infusion until disease progression, start of a new anticancer therapy, or death due to any cause, whichever occurs first [up to a maximum of 5 calendar years after the lifileucel infusion]).
- 2. CR rate is defined as the proportion of participants who have a confirmed CR per RECIST v1.1 from the date of the lifileucel infusion until disease progression, start of a new anticancer therapy, or death due to any cause, whichever occurs first (up to a maximum of 5 calendar years after the lifileucel infusion).
- 3. DOR is measured from the first time that criteria are met for CR or PR per RECIST v1.1 until disease progression or death due to any cause (up to a maximum of 5 calendar years after the lifileucel infusion).
- 4. DCR is measured by the percentage of participants with a best overall confirmed response of CR or PR at any time or SD ≥ 4 weeks per RECIST v1.1 from the date of the lifileucel infusion until disease progression, start of a new anticancer therapy, or death due to any cause, whichever occurs first (up to a maximum of 5 calendar years after the lifileucel infusion).
- 5. PFS is defined as the time from the date of the lifileucel infusion until disease progression per RECIST v1.1 or death due to any cause (up to a maximum of 5 calendar years after the lifileucel infusion).
- 6. OS is the time from the date of the lifileucel infusion to death due to any cause (up to a maximum of 5 calendar years after the lifileucel infusion).
- 7. The safety of lifileucel will be characterized by the severity, seriousness, relationship to study intervention, and characteristics of REAE and TEAEs, including SAEs, study intervention-related AEs, and AEs leading to early discontinuation of study intervention or death (event monitoring periods will be defined based on the type of event).
研究者
Guy Ruble
Scientific
Iovance Biotherapeutics Inc.
研究点 (18)
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