A Study to Investigate the Safety and Efficacy of IOV-3001 in Adults With Advanced Melanoma Who Will Receive Lifileucel

This study is the first-in-human (FIH) study of IOV-3001. IOV-3001 is an antibody interleukin-2 (IL-2) fusion protein in which a modified form of aldesleukin is incorporated into the antibody palivizumab.

The Phase 1 portion will include 2 parts. Participants will receive IOV-3001 either before the Lifileucel regimen (Part 1) or after Lifileucel instead of aldesleukin (Part 2).

Inclusion criteria

• Participant must be ≥ 18 years of age at the time of signing the informed consent.
• Participant has unresectable or metastatic melanoma.
• Participant has melanoma not of uveal/ocular origin and experienced documented radiographic disease progression during systemic therapy with a PD-1/PD-L1 blocking antibody or within 12 weeks after the last dose of the PD-1/PD-L1 blocking antibody. If the tumor is BRAF V600 mutation positive, the participant also received or refused a BRAF inhibitor with or without a MEK inhibitor.

OR Phase 1, Part 1 only: For participants with uveal melanoma, tebentafusp must have been received if available as standard of care (human leukocyte antigen [HLA]-A*02:01 positive participant and approved by local authorities for uveal melanoma) or refused.

• Participant has an ECOG performance status of 0 or 1 and, in the investigator's opinion, an estimated life expectancy of > 6 months.
• Phase 1, Part 2 only: Following tumor resection for lifileucel generation, the participant will have at least one remaining measurable lesion, as defined by RECIST v1.1.
• Participant has recovered from all prior anticancer treatment-related AEs

Exclusion criteria

• Participant has symptomatic untreated brain metastases.
• Participant is at an increased risk for systemic infections; seizure disorders; coagulation disorders; or other active major medical illnesses of the cardiovascular, respiratory, or immune systems.
• Participant has active uveitis that requires active treatment.
• Participant has any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease [SCID] or AIDS).
• Participant has a history of hypersensitivity to any component of the study intervention.
• Participant had another primary malignancy within the previous 3 years.
• Participants who require systemic steroid therapy 10 mg/day prednisone or another steroid equivalent dose.
• Participants who have had a history of allogeneic organ transplant or any form of cell therapy involving prior conditioning chemotherapy within the past 20 years.