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.

Study Description

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

• 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

Arms and Interventions

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

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

• 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

Contacts

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

Locations

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

Moffitt Cancer Center; Recruiting

Tampa, Florida, United States, 33612

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

• Study Director: Iovance Biotherapeutics Study Team; Iovance Biotherapeutics

More Information

• Responsible Party: Iovance Biotherapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05361174
• Other Study ID Numbers: IOV-GM1-201
• First Posted: May 4, 2022
• Last Update Posted: August 22, 2023
• Last Verified: August 2023

• 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:

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; Skin Neoplasms; Skin Diseases