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

Официальное название

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

Обзор

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).

Подробное описание

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).

Вмешательства

• Биопрепарат 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.

Первичные конечные точки

• Phase I: Safety of IOV-4001 [Срок оценки: Up to 1 Year or depending on when the recommended phase 2 dose is determined]
• Phase 2: Objective Response Rate (ORR) [Срок оценки: Up to 60 months]

Вторичные конечные точки (7)

• CR Rate [Срок оценки: Up to 60 months]
• Duration of Response (DOR) [Срок оценки: Up to 60 months]
• Disease Control Rate (DCR) [Срок оценки: Up to 60 months]
• Progression-free Survival (PFS) [Срок оценки: Up to 60 months]
• Overall Survival (OS) [Срок оценки: Up to 60 months]
• Safety and Tolerability of IOV-4001 [Срок оценки: Up to 60 months]
• Feasibility of IOV-4001 [Срок оценки: Up to 60 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 11 центров

• The Angeles Clinic and Research Institute — Los Angeles
• Sylvester Comprehensive Cancer Center — Miami
• Orlando Health Cancer Institute — Orlando
• Moffitt Cancer Center — Tampa
• The University of Kansas Cancer Center — Westwood
• University of Louisville — Louisville
• Weill Medical College of Cornell University — New York
• Memorial Sloan Kettering Cancer Center — New York
• … и ещё 3 центра

Идентификаторы

NCT: NCT05361174 · IOV-GM1-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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