Lifileucel (TIL) Therapy After PD-1 Blockade Failure in Kidney Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed, advanced or metastatic renal cell carcinoma with clear cell, papillary, sarcomatoid (with or without other subtypes present), or unclassified histology. Other non-clear cell subtypes are also eligible if the patient has had a prior documented response to immune checkpoint inhibitor therapy.

  • Participants must have measurable disease with at least two malignant lesions, one for disease monitoring as response to therapy and one for TIL harvest.
  • Age ≥18 years
  • Received one of the following regimens:
  • Anti-PD-(L)1 immune checkpoint inhibitor (ICI) with or without an anti-CTLA-4 ICI or VEGF tyrosine kinase inhibitor (TKI) for treatment of advanced/metastatic disease, and experienced either (1) radiographic progression of disease while on treatment or (2) best response of stable disease after at least 6 months
  • Adjuvant anti-PD-(L)1 ICI after nephrectomy for localized disease and had either (1) disease recurrence while receiving adjuvant ICI or (2) disease recurrence within 6 months of the final dose of any amount of adjuvant ICI
  • Prior HIF2α inhibitor exposure in the adjuvant or advanced/metastatic setting is allowed but not required
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of ≥ 3 months in the opinion of the Investigator.
  • Participants must have adequate organ and marrow function as defined in the protocol.
  • Patients with definitively treated brain metastases may be considered for enrollment if the patient is clinically stable for ≥ 14 days, with no lesions on follow-up imaging and no requirement for ongoing steroid treatment.
  • Participants must have a washout period from any anticancer therapy prior to tumor harvest. The protocol contains provisions for optional use of "bridging" TKI between tumor harvest and lymphodepleting chemotherapy.
  • Palliative radiation therapy is permitted as long as it does not involve lesions being selected for resection for TIL manufacturing, or being assessed radiographically as target lesions.
  • Participants must have recovered from all prior anti-cancer therapy-related adverse events (AEs), as defined in the protocol.
  • Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control.
  • Previous surgical procedure(s) is/are permitted provided that wound healing has occurred, all complications have resolved, and at least 14 days have elapsed (for major operative procedures) prior to the tumor resection.

Exclusion Criteria:

• Patients who have received an organ allograft or prior cell transfer therapy within the past 20 years that included a non-myeloablative or myeloablative chemotherapy regimen.
• Patients who have a history of hypersensitivity to any component of the study intervention.
• Patients with rapidly progressive disease or symptomatic disease requiring urgent treatment per investigator discretion.
• Patients with symptomatic and/or untreated brain metastases.
• Patients who are on chronic systemic steroid therapy except for those requiring steroid therapy for management of adrenal insufficiency.
• Patients who are pregnant or breastfeeding.
• Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency disease [SCID] and acquired immunodeficiency syndrome [AIDS]).
• Patients with any other primary malignancy that is radiographically visible or is expected to require treatment within the next three years.
• Patients who are hypoxemic (oxygen saturation <90%) on room air at baseline or who require supplemental oxygen.

Other protocol-defined inclusion/exclusion criteria may apply.