RecruitingPhase 1Phase 2NCT05361174

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

Sponsor

Iovance Biotherapeutics, Inc.

Enrollment

53 participants

Start Date

Jul 20, 2022

Study Type

INTERVENTIONAL

Conditions

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

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).

Eligibility

Min Age: 18 YearsMax Age: 70 Years

Inclusion Criteria16

Participants must have a confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma or Stage III or IV NSCLC.
Participants who have received the following previous therapy:
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.
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
Participants who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Participants who is assessed as having at least one resectable lesion.
Participants who have at least one measurable lesion, following resection of the lesion for IOV-4001 generation.
Participants who have adequate organ function.
Cardiac function test required.
Pulmonary function test may be required.
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.
Participants who are \>70 years of age may be allowed to enroll after the investigator discusses with the medical monitor.

Exclusion Criteria7

Participants who have melanoma of uveal/ocular origin.
Participants who have symptomatic untreated brain metastases.
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.
Participants who require systemic steroid therapy 10 mg/day prednisone or another steroid equivalent dose.
Participants who have any form of primary immunodeficiency.
Participants who have another primary malignancy within the previous 3 years.
Participants who have received or will receive a live or attenuated vaccination within 28 days prior to the start of the NMA-LD.

Interventions

BIOLOGICALIOV-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.