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A Study to Investigate the Efficacy and Safety of an Infusion of IOV-4001 in Adult Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05361174
Recruitment Status : Recruiting
First Posted : May 4, 2022
Last Update Posted : March 31, 2023
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

Study Description
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Brief 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).

Condition or disease Intervention/treatment Phase
Unresectable Melanoma Metastatic Melanoma Stage III Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer Biological: IOV-4001 Phase 1 Phase 2

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).
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 20, 2022
Estimated Primary Completion Date : June 2025
Estimated Study Completion Date : June 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1
Participants with unresectable or metastatic melanoma
 Biological: IOV-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.
Experimental: Cohort 2
Participants with Stage III or IV non-small-cell lung cancer
 Biological: IOV-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
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Primary Outcome Measures :
  1. Phase I: Safety of IOV-4001 [ Time Frame: Up to 1 Year or depending on when the recommended phase 2 dose is determined ]
    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

  2. Phase 2: Objective Response Rate (ORR) [ Time Frame: Up to 60 months ]
    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


Secondary Outcome Measures :
  1. CR Rate [ Time Frame: Up to 60 months ]
    To evaluate the proportion of participants who have a confirmed CR per RECIST v1.1 as assessed by the investigator

  2. Duration of Response (DOR) [ Time Frame: Up to 60 months ]
    To evaluate the duration from the time that criteria are met for CR or PR per RECIST v1.1 as assessed by the investigator until disease progression or death due to any cause

  3. Disease Control Rate (DCR) [ Time Frame: Up to 60 months ]
    To evaluate the percentage of participants with a best overall confirmed response of CR or PR at any time plus stable disease (SD) per RECIST v1.1 as assessed by the investigator

  4. Progression-free Survival (PFS) [ Time Frame: Up to 60 months ]
    To evaluate the time from the date of IOV-4001 infusion until disease progression per RECIST v1.1 as assessed by the investigator or death due to any cause

  5. Overall Survival (OS) [ Time Frame: Up to 60 months ]
    To evaluate the time from the date of IOV-4001 infusion to death due to any cause.

  6. Safety and Tolerability of IOV-4001 [ Time Frame: Up to 60 months ]
    This will be characterized by the severity, seriousness, relationship to study treatment, and characteristics of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), study intervention-related adverse events (AEs), and AEs.

  7. Feasibility of IOV-4001 [ Time Frame: Up to 60 months ]
    This will be assessed by the proportion of participants who had tumor harvested and were treated without manufacturing delay or failure.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participants must have a confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma (Cohort 1) or Stage III or IV NSCLC (Cohort 2).

  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.

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05361174


Contacts
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Contact: Iovance Biotherapeutics Study Team 866-565-4410 Clinical.Inquiries@iovance.com

Locations
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United States, California
The Angeles Clinic and Research Institute Recruiting
Los Angeles, California, United States, 90025
United States, Florida
Orlando Health Cancer Institute Recruiting
Orlando, Florida, United States, 32610
United States, Kansas
The University of Kansas Cancer Center Recruiting
Westwood, Kansas, United States, 66205
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45219
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Iovance Biotherapeutics, Inc.
Investigators
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Study Director: Iovance Biotherapeutics Study Team Iovance Biotherapeutics
More Information
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Responsible Party: Iovance Biotherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05361174    
Other Study ID Numbers: IOV-GM1-201
First Posted: May 4, 2022    Key Record Dates
Last Update Posted: March 31, 2023
Last Verified: March 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Iovance Biotherapeutics, Inc.:
Tumor Infiltrating Lymphocytes
TIL
Unresectable Melanoma
Metastatic Melanoma
Stage III Non-small-cell lung cancer
Stage IV Non-small-cell lung cancer
PD-1 Knockout
Cell Therapy
Autologous Adoptive Cell Therapy
Cellular Immuno-therapy
IL-2
Non Small Cell Lung Cancer
NSCLC
Second line Lung Cancer
Bronchial Neoplasms
 Carcinoma
Lung Disease
Metastatic Lung Cancer
Metastatic Non Small Cell Lung Cancer
Lung Carcinoma
PD-L1
Stage IV Cancer
Stage IV Lung Cancer
Stage IV NSCLC
Systemic Therapy
2nd line therapy
Second line therapy
CPI
Check point inhibitor
Metastatic NSCLC
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Melanoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
 Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas