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
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).
Arms & 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.
Outcome measures
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
Time frame: Up to 1 Year or depending on when the recommended phase 2 dose is determined
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
Time frame: Up to 60 months
Secondary
CR Rate
Time frame: Up to 60 months
Duration of Response (DOR)
Time frame: Up to 60 months
Disease Control Rate (DCR)
Time frame: Up to 60 months
Progression-free Survival (PFS)
Time frame: Up to 60 months
Overall Survival (OS)
Time frame: Up to 60 months
Safety and Tolerability of IOV-4001
Time frame: Up to 60 months
Feasibility of IOV-4001
Time frame: Up to 60 months
Eligibility criteria
Study locations (11)
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Orlando Health Cancer Institute
Orlando, Florida, 32610
Moffitt Cancer Center
Tampa, Florida, 33612
The University of Kansas Cancer Center
Westwood, Kansas, 66205
University of Louisville
Louisville, Kentucky, 40202
Weill Medical College of Cornell University
New York, New York, 10022
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Cincinnati
Cincinnati, Ohio, 45219
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226