Infusion of IOV-4001 for advanced melanoma and lung cancer

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

Phase1; Phase2 Interventional Iovance Biotherapeutics, Inc. · NCT05361174

This study is testing a new treatment called IOV-4001 to see if it can help adults with advanced melanoma and lung cancer by targeting and killing their tumor cells.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment53 (estimated)
Ages18 Years to 70 Years
SexAll
SponsorIovance Biotherapeutics, Inc. Industry-sponsored
Drugs / interventionschemotherapy, prednisone
Locations10 sites (Los Angeles, California and 9 other locations)
Trial IDNCT05361174 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of IOV-4001, a genetically modified autologous tumor-infiltrating lymphocyte (TIL) product, in adult patients with unresectable or metastatic melanoma and advanced non-small-cell lung cancer (NSCLC). The study aims to assess how well IOV-4001 can target and kill tumor cells, potentially offering enhanced antitumor activity by disrupting the PDCD1 gene associated with programmed cell death protein-1 (PD-1). Participants will receive the infusion and be monitored for safety and effectiveness.

Who should consider this trial

Good fit: Ideal candidates include adults with unresectable or metastatic melanoma or Stage III/IV non-small-cell lung cancer who have progressed after standard therapies.

Not a fit: Patients who have not received prior therapies or those with early-stage cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced melanoma and lung cancer who have limited treatment alternatives.

How similar studies have performed: Other studies using tumor-infiltrating lymphocytes have shown promise, suggesting potential for success with this novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria
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.

Where this trial is running

Los Angeles, California and 9 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Unresectable MelanomaMetastatic MelanomaStage III Non-small Cell Lung CancerStage IV Non-small Cell Lung CancerTumor Infiltrating LymphocytesTILStage III Non-small-cell lung cancerStage IV Non-small-cell lung cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.