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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Melanoma; Unresectable Melanoma; Stage IV Non-small Cell Lung Cancer; Stage III Non-small Cell Lung Cancer
• Intervention / Treatment: Biological: IOV-4001

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 Type: Interventional
• Enrollment (Estimated): 53
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • Recruiting
      • The Angeles Clinic and Research Institute
  • Florida
    • Orlando, Florida, United States, 32610
      • Recruiting
      • Orlando Health Cancer Institute
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Recruiting
      • The University of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR Rate	To evaluate the proportion of participants who have a confirmed CR per RECIST v1.1 as assessed by the investigator	Up to 60 months
Duration of Response (DOR)	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	Up to 60 months
Disease Control Rate (DCR)	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	Up to 60 months
Progression-free Survival (PFS)	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	Up to 60 months
Overall Survival (OS)	To evaluate the time from the date of IOV-4001 infusion to death due to any cause.	Up to 60 months
Safety and Tolerability of IOV-4001	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.	Up to 60 months
Feasibility of IOV-4001	This will be assessed by the proportion of participants who had tumor harvested and were treated without manufacturing delay or failure.	Up to 60 months

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): July 20, 2022
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Cell Therapy; NSCLC; Carcinoma; Non Small Cell Lung Cancer; Melanoma; Malignant melanoma; Skin cancer; PD-L1; Systemic Therapy; Tumor Infiltrating Lymphocytes; IL-2; Lung Disease; TIL; Bronchial Neoplasms; Autologous Adoptive Cell Transfer; Autologous Adoptive Cell Therapy; Cellular Immuno-therapy; Lifileucel; Metastatic Melanoma; Unresectable Melanoma; Stage IV Melanoma; CPI; Stage III Melanoma; Metastatic NSCLC; Check point inhibitor; Metastatic Non Small Cell Lung Cancer; PD-1 Knockout; Metastatic Lung Cancer; Stage IV NSCLC; Second line therapy; Lung Carcinoma; Stage III Non-small-cell lung cancer; Stage IV Non-small-cell lung cancer; Second line Lung Cancer; Stage IV Cancer; Stage IV Lung Cancer; 2nd line therapy; NSCLC Recurrent; Recurrent Lung Cancer; Recurrent Lung Carcinoma; Skin cancer types
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma
• Other Study ID Numbers: IOV-GM1-201

Drug and device information, study documents

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