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

A Phase 1/2, Open-label Study of a Modified Interleukin-2 Fusion Protein (IOV-3001) in Participants With Previously Treated, Unresectable or Metastatic Melanoma Who Will Receive Lifileucel

A Phase 1/2, open-label study of a modified interleukin-2 fusion protein (IOV 3001) in participants with previously treated, unresectable or metastatic melanoma who will receive lifileucel.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Melanoma; Ocular Melanoma; Unresectable Melanoma
• Intervention / Treatment: Biological: IOV-3001

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Iovance Biotherapeutics; Phone Number: 1-844-845-4682; Email: Clinical.Inquiries@iovance.com

Study Locations

• Australia
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Recruiting
      • Greenslopes Private Hospital
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • SCRI Oncology Partners- Denver
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • UNC Hospitals, The University of North Carolina at Chapel Hill
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant must be ≥ 18 years of age at the time of signing the informed consent.
2. Participant has unresectable or metastatic melanoma.

3. 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.

4. Participant has an ECOG performance status of 0 or 1 and, in the investigator's opinion, an estimated life expectancy of > 6 months.
5. 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.
6. Participant has recovered from all prior anticancer treatment-related AEs

Exclusion Criteria:

1. Participant has symptomatic untreated brain metastases.
2. 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.
3. Participant has active uveitis that requires active treatment.
4. Participant has any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease [SCID] or AIDS).
5. Participant has a history of hypersensitivity to any component of the study intervention.
6. Participant had another primary malignancy within the previous 3 years.
7. Participants who require systemic steroid therapy 10 mg/day prednisone or another steroid equivalent dose.
8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Assigned Interventions; Dose escalation participants with unresectable or metastatic melanoma	Biological: IOV-3001; IOV-3001 will be administered as a single dose by IV infusion, which will be administered in a hospital setting.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	The frequency and severity of treatment emergent adverse events and serious adverse events will be assessed when IOV-3001 administered	Up to 30 days
Recommended Dose for Phase 2	Determine the recommended dose for Phase 2	Up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as the proportion of participants who have a confirmed CR or PR per RECIST v1.1 as assessed by the investigator from the date of lifileucel infusion until disease progression, start of a new anticancer therapy, or death due to any cause cause, whichever occurs first (up to a maximum of 5 years after the lifileucel infusion)	Up to 5 years
Complete Response (CR) rate	CR rate is defined as the proportion of participants who have a confirmed CR per RECIST v1.1 as assessed by the investigator from the date of lifileucel infusion until disease progression, start of a new anticancer therapy, or death due to any cause cause (up to a maximum of 5 years after the lifileucel infusion)	Up to 5 years
Duration of Response (DOR)	DOR is measured from the time that criteria are met for CR or PR per RECIST v1.1 as assessed by the investigator disease progression or death due to any cause (up to a maximum of 5 years after the lifileucel infusion)	Up to 5 years
Disease Control Rate (DCR)	DCR is measured by the percentage of participants with a best overall confirmed response of CR or PR at any time participants with SD ≥ 4 weeks per RECIST v1.1 as assessed by the investigator from the date of lifileucel infusion disease progression, start of a new anticancer therapy, or death due to any cause (up to a maximum of 5 years after the lifileucel infusion)	Up to 5 years
Progression-Free Survival (PFS)	PFS is defined as the time from the date of lifileucel infusion until disease progression per RECIST v1.1 as assessed by investigator or death due to any cause (up to a maximum of 5 years after the lifileucel infusion)	Up to 5 years
Overall Survival (OS)	OS is the time from the date of lifileucel infusion to death due to any cause (up to a maximum of 5 years after the lifileucel infusion)	Up to 5 years
Pharmacokinetics (PK) profile of IOV-3001	PK as measured by maximum observed drug concentration in plasma (Cmax) after single dose, and area under the concentration vs. time curve (AUC) after single dose.	Up to 8 days
Pharmacodynamic (PD) Profile of IOV-3001	The PD profile will be assessed by evaluating changes in the expression of phenotypic markers, serum cytokines and chemokines in blood.	Up to 8 days
Antidrug Antibody (ADA) Profile	ADAs to IOV-3001 will be measured in blood.	Up to 5 years
In vivo persistence of Lifileucel	In vivo persistence of lifileucel products will be assessed in the blood.	Up to 5 years

Collaborators and Investigators

• Sponsor: Iovance Biotherapeutics, Inc.
• Investigators: Study Director: Iovance Biotherapeutics Study Team, Iovance Biotherapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2025
• Primary Completion (Estimated): June 1, 2032
• Study Completion (Estimated): July 1, 2032

Study Registration Dates

• First Submitted: April 8, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 23, 2025

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Cell Therapy; Melanoma; Tumor Infiltrating Lymphocytes; IL-2; Uveal Melanoma; TIL; Autologous Adoptive Cell Transfer; Autologous Adoptive Cell Therapy; Cellular Immuno-therapy; Lifileucel; Metastatic Melanoma; Malignant Melanoma; Unresectable Melanoma; Stage IV Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Eye Diseases; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Eye Neoplasms; Uveal Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Melanoma; Uveal Melanoma
• Other Study ID Numbers: IOV-IL2-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No