Clinical trial NCT05361174: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Unresectable Melanoma
Metastatic Melanoma
Stage III Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Keywords: 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
NSCLC Recurrent
Recurrent Lung Cancer
Recurrent Lung Carcinoma
Autologous Adoptive Cell Transfer
Melanoma
Lifileucel
Stage III Melanoma
Stage IV Melanoma
Skin cancer
Skin cancer types
Malignant melanoma
Lead sponsor: Iovance Biotherapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-04
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Phase I: Safety of IOV-4001
timeFrame: Up to 1 Year or depending on when the recommended phase 2 dose is determined
measure: Phase 2: Objective Response Rate (ORR)
timeFrame: Up to 60 months
Secondary outcomes:
measure: CR Rate
timeFrame: Up to 60 months
measure: Duration of Response (DOR)
timeFrame: Up to 60 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 60 months
measure: Progression-free Survival (PFS)
timeFrame: Up to 60 months
measure: Overall Survival (OS)
timeFrame: Up to 60 months
measure: Safety and Tolerability of IOV-4001
timeFrame: Up to 60 months
measure: Feasibility of IOV-4001
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Iovance Biotherapeutics
name: Iovance Biotherapeutics Study Team
role: STUDY_DIRECTOR
References: