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

Phase 1

Recruiting

• Conditions: Unresectable Melanoma; Stage III Non-small Cell Lung Cancer; Metastatic Melanoma; Stage IV Non-small Cell Lung Cancer
• Interventions: Biological: IOV-4001

• Registration Number: NCT05361174
• Lead Sponsor: Iovance Biotherapeutics, Inc.

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 Timeline

• Study First Submitted: 2022-04-29
• Study First Submitted QC: 2022-04-29
• Study First Posted: 2022-05-04
• Study Start: 2022-07-20
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-05
• Primary Completion: 2025-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

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

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.

10. Participants who are >70 years of age may be allowed to enroll after the investigator discusses with the medical monitor.

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	IOV-4001	Participants with unresectable or metastatic melanoma
Cohort 2	IOV-4001	Participants with Stage III or IV non-small-cell lung cancer

Primary Outcome Measures

Name	Time	Method
Phase 2: Objective Response Rate (ORR)	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
Phase I: Safety of IOV-4001	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

Secondary Outcome Measures

Name	Time	Method
CR Rate	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)	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)	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)	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)	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	Up to 60 months	This will be characterized by the severity, seriousness, relationship to study treatment, and characteristics of treatment-emergent adverse events (TEAEs).
Feasibility of IOV-4001	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.

Trial Locations

Locations (10)

The Angeles Clinic and Research Institute; 🇺🇸 Los Angeles, California, United States

Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, 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, United States

University of Louisville; 🇺🇸 Louisville, Kentucky, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States