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

Metastatic Melanoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05361174
• Other study ID #: IOV-GM1-201
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 20, 2022
• Est. completion date: June 2027

Study information

• Verified date: August 2023
• Source: Iovance Biotherapeutics, Inc.
• Contact: Iovance Biotherapeutics Study Team
• Phone: 1-844-845-4682
• Email: Clinical.Inquiries[@]iovance.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 53
• Est. completion date: June 2027
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Melanoma
• Metastatic Melanoma
• Stage III Non-small Cell Lung Cancer
• Stage IV Non-small Cell Lung Cancer
• Unresectable Melanoma

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.

Locations

Country	Name	City	State
United States	University of Cincinnati	Cincinnati	Ohio
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Moffitt Cancer Center	Tampa	Florida
United States	The University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Iovance Biotherapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall Survival (OS)	To evaluate the time from the date of IOV-4001 infusion to death due to any cause.	Up to 60 months
Secondary	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
Secondary	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