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RecruitingInterventionalPhase 1/Phase 2

A Phase 1/2, Open-label Study of PD-1 Knockout Tumor-infiltrating Lymphocytes (IOV-4001) in Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer

NCT ID: NCT05361174Sponsor: Iovance Biotherapeutics, Inc.Last updated: 2026-06-11

Summary

This is a study to investigate the efficacy and safety of an infusion of IOV-4001 in adult participants with unresectable or metastatic melanoma or advanced non-small-cell lung cancer (NSCLC).

Detailed description

This study is the first-in-human study of IOV-4001, a genetically modified autologous tumor- infiltrating lymphocytes (TIL) product. IOV-4001 is expected to have antitumor activity through its capacity to directly target and kill tumor cells in a manner that is similar to non-genome-edited TIL, but with the potential for enhanced antitumor activity due to disruption of PDCD1, the gene for programmed cell death protein-1 (PD-1).

Arms & interventions

  • BiologicalIOV-4001

    A tumor sample is resected from each participant and cultured ex-vivo to manufacture IOV-4001. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, participant is infused with IOV-4001, and followed by IL-2.

Outcome measures

Primary

  • Phase I: Safety of IOV-4001

    The safety of IOV-4001 will be assessed based on the totality of dose-limiting toxicity (DLT) and adverse event (AE) data collected during this phase

    Time frame: Up to 1 Year or depending on when the recommended phase 2 dose is determined

  • Phase 2: Objective Response Rate (ORR)

    To evaluate the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by the investigator

    Time frame: Up to 60 months

Secondary

  • CR Rate

    Time frame: Up to 60 months

  • Duration of Response (DOR)

    Time frame: Up to 60 months

  • Disease Control Rate (DCR)

    Time frame: Up to 60 months

  • Progression-free Survival (PFS)

    Time frame: Up to 60 months

  • Overall Survival (OS)

    Time frame: Up to 60 months

  • Safety and Tolerability of IOV-4001

    Time frame: Up to 60 months

  • Feasibility of IOV-4001

    Time frame: Up to 60 months

Eligibility criteria

Sex: AllAge: 18 Years to 70 YearsHealthy volunteers: No
Inclusion Criteria: 1. Participants must have a confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma or Stage III or IV NSCLC. 2. Participants who have received the following previous therapy: 1. Cohort 1 (Melanoma): Participants who have progressed within 12 weeks of last dose of anti-PD-1/PD-L1 blocking antibody and received BRAF/MEK inhibitor in those with BRAF mutations. 2. Cohort 2 (NSCLC): Participants who should have received no more than 3 prior lines of therapy and: * those without oncogene-driven tumors: Have progressed within 12 weeks after last dose of anti-PD-1/PD-L1 blocking antibody * those with oncogene-driven tumors: Have progressed during/after ≥1 targeted therapy AND either: * platinum doublet chemotherapy * Or within 12 weeks after last dose of anti-PD-1/PD-L1 blocking antibody 3. Participants who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. Participants who is assessed as having at least one resectable lesion. 5. Participants who have at least one measurable lesion, following resection of the lesion for IOV-4001 generation. 6. Participants who have adequate organ function. 7. Cardiac function test required. 8. Pulmonary function test may be required. 9. Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and up to 12 months. 10. Participants who are \>70 years of age may be allowed to enroll after the investigator discusses with the medical monitor. Exclusion Criteria: 1. Participants who have melanoma of uveal/ocular origin. 2. Participants who have symptomatic untreated brain metastases. 3. 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. 4. Participants who require systemic steroid therapy 10 mg/day prednisone or another steroid equivalent dose. 5. Participants who have any form of primary immunodeficiency. 6. Participants who have another primary malignancy within the previous 3 years. 7. Participants who have received or will receive a live or attenuated vaccination within 28 days prior to the start of the NMA-LD.

Study locations (11)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025

Recruiting

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136

Recruiting

Orlando Health Cancer Institute

Orlando, Florida, 32610

Recruiting

Moffitt Cancer Center

Tampa, Florida, 33612

Recruiting

The University of Kansas Cancer Center

Westwood, Kansas, 66205

Recruiting

University of Louisville

Louisville, Kentucky, 40202

Recruiting

Weill Medical College of Cornell University

New York, New York, 10022

Recruiting

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting

University of Cincinnati

Cincinnati, Ohio, 45219

Recruiting

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

Recruiting

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

Withdrawn