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

• ClinicalTrials.gov Identifier: NCT05361174
• Recruitment Status: Recruiting
• First Posted: May 4, 2022
• Last Update Posted: August 22, 2023
• Sponsor: Iovance Biotherapeutics, Inc.
• Information provided by (Responsible Party): Iovance Biotherapeutics, Inc.

Tracking Information

• First Submitted Date: April 29, 2022
• First Posted Date: May 4, 2022
• Last Update Posted Date: August 22, 2023
• Actual Study Start Date: July 20, 2022
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 29, 2022)

• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 29, 2022)

• 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
• 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
• 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
• 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
• 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.
• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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).
• 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
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Unresectable Melanoma
• Metastatic Melanoma
• Stage III Non-small Cell Lung Cancer
• Stage IV Non-small Cell Lung Cancer

Intervention

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.

Study Arms

• Experimental: Cohort 1
  Participants with unresectable or metastatic melanoma
  Intervention: Biological: IOV-4001
• Experimental: Cohort 2
  Participants with Stage III or IV non-small-cell lung cancer
  Intervention: Biological: IOV-4001

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 29, 2022): 53
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2027
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Iovance Biotherapeutics Study Team; 1-844-845-4682; Clinical.Inquiries@iovance.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05361174
• Other Study ID Numbers: IOV-GM1-201
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Iovance Biotherapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Iovance Biotherapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Iovance Biotherapeutics Study Team; Iovance Biotherapeutics

• PRS Account: Iovance Biotherapeutics, Inc.
• Verification Date: August 2023