Replaying this post as a reminder that this study is enrolling at multiple sites globally. More detailed information can also be seen here at clinicaltrials.gov as well as the sponsor Iovance. All information and data stated in this article are available publicly through online resources that I’ve also linked below for reference. This new trial will combine cellular therapy with checkpoint inhibitors in the first line setting for metastatic melanoma. Those who are on the checkpoint inhibitor alone arm will have the option to pursue or cross over to TIL cellular therapy at the time of progression. Currently, Lifileucel has not been FDA approved and is currently under review.
In the war against cancer, advanced melanoma has long stood as one of the fiercest adversaries. Despite promising advancements in the field of immunotherapy, a large percentage of patients find themselves locked in a battle that their current treatments can’t win. As we grapple with this reality, we are driven to uncover new, more effective ways to outsmart this ruthless disease. Enter lifileucel (LN-144), a novel therapy that has burst onto the scene, demonstrating impressive results in recent studies and inspiring hope for melanoma patients worldwide. Let’s dive into Tumor-Infiltrating Lymphocyte (TIL) therapy that have led us to this pivotal moment in melanoma treatment, and explore the exciting frontier of the TILVANCE-301 trial.
In the quest for solutions, Tumor-Infiltrating Lymphocytes (TIL) therapy has emerged as a promising option. TIL therapy is a personalized treatment approach, involving the cultivation and expansion of a patient’s own T lymphocytes taken from their tumor, stimulated with interleukin-2 before being returned to the patient’s body. Initial applications were complex and time-consuming, but innovations have streamlined the process, leading to wider testing and more reproducible results. Meta-analyses have shown response rates between 28% and 45% among patients receiving TIL therapy.
It’s important to note that these findings largely preceded the approval of first-line PD-1 blockade therapy for advanced melanoma and several biotech companies have improved the TIL product turnaround time to about 3-6 weeks making it more palatable for patients and healthcare providers to consider. Since then, a crucial question arose: Could patients whose disease was refractory to newer treatments such as anti-PD-1 plus or minus anti-CTL4 therapy benefit from TIL therapy? An Iovance Phase 2, multi-center study of TIL therapy answered this question affirmatively, reporting a response rate of 36%, with 80% disease control. In addition, a second line randomized study in NEJM 2022 demonstrated improved overall survival in PD1-refractory patients with the use of 2nd line TIL compared to those who just received standard of care ipilimumab alone. In the first line setting of previously untreated patients, a small phase 2 trial showed an overall response rate of 86% with the combination lifileucel and pembrolizumab, a promising development compared to historical responses seen with single-agent therapies.
These exciting results underscore the potential of TIL therapy and point to a synergistic relationship when combined with PD-1 inhibitors. The new TILVANCE-301 Phase 3 study aims to assess the efficacy and safety of lifileucel combined with pembrolizumab, as compared to standard of care pembrolizumab alone in untreated unresectable or metastatic melanoma. The trial will provide crucial data to inform the ongoing debate about the appropriate sequence and combination of therapies for advanced melanoma. Notably, the TILVANCE-301 trial offers patients who do not respond to pembrolizumab the opportunity to switch or crossover to lifileucel monotherapy, providing an added layer of therapeutic adaptability and availability that would otherwise not be available to the patient. TIL monotherapy in refractory melanoma patients is currently under FDA review.
As we look forward, we’re reminded of how far we’ve come in treating advanced melanoma. From the foundational studies exploring the effectiveness of TIL therapy to the ongoing TILVANCE-301 trial, we continue to push the boundaries of what’s possible in cancer treatment. This study is now open and enrolling at select sites across the country.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.