What Is Lifileucel?
Lifileucel is an investigational cell therapy being studied for various cancers. It is a type of immunotherapy that uses a patient's own immune cells, specifically tumor-infiltrating lymphocytes (TILs), to fight cancer. The process involves resecting a tumor sample from the patient, from which TILs are isolated and expanded in a laboratory to significantly increase their numbers. Before the infusion of these expanded TILs, patients typically undergo a preparative non-myeloablative lymphodepletion regimen. Following the lifileucel infusion, patients often receive a course of aldesleukin or interleukin-2 (IL-2) to support the activity of the infused cells. In some studies, lifileucel is administered in combination with other immunotherapies like pembrolizumab.
Currently, lifileucel is being investigated in clinical trials for conditions such as metastatic melanoma, unresectable melanoma, and other forms of melanoma. It is also being studied for non-small cell lung cancer and squamous cell carcinoma of the head and neck. A total of 10 trials have been conducted or are ongoing, with 6 trials currently recruiting participants.
Uses and Conditions Under Study
Lifileucel is primarily under investigation for the treatment of various types of melanoma. These include metastatic melanoma, which is melanoma that has spread to other parts of the body, and unresectable melanoma, meaning the cancer cannot be removed surgically. It is also being studied for specific stages of cutaneous melanoma, such as Pathologic Stage IIIB, IIIC, and IIID, as well as cutaneous malignant melanoma and metastatic uveal melanoma. The drug's mechanism, which involves enhancing the body's own immune response against tumor cells, is being explored to determine its effectiveness in these challenging forms of skin cancer. There are 7 trials specifically studying metastatic melanoma, and a total of 10 trials involving various melanoma types.
Beyond melanoma, lifileucel is also being evaluated for its potential in other solid tumors. One trial is investigating lifileucel for non-small cell lung cancer, a common type of lung cancer. Another trial is exploring its use in squamous cell carcinoma of the head and neck, a type of cancer that begins in the flat cells lining the moist surfaces inside the head and neck. These studies aim to see if the tumor-infiltrating lymphocyte therapy approach can be broadly effective across different cancer types where immune evasion is a significant factor.
Dosing
Information regarding specific dosage forms and strengths for lifileucel is not detailed in the provided trial data. However, based on the drug descriptions, lifileucel is administered as an infusion. The treatment regimen typically involves several steps: first, a preparative non-myeloablative lymphodepletion (NMA-LD) regimen is given to the patient. This prepares the body for the incoming immune cells. Next, the lifileucel infusion is administered. Following the infusion, patients usually receive an abbreviated course of aldesleukin or interleukin-2 (IL-2) for up to 10 days, which helps support the activity and growth of the infused tumor-infiltrating lymphocytes.
Clinical trials have explored various treatment approaches and combinations. For example, some studies investigate lifileucel as a standalone therapy, while others combine it with additional medications such as pembrolizumab. The trial data describes various study arms and cohorts, such as "Single Arm," "Experimental arm," "Control arm- investigator's choice," and specific cohorts like "Cohort 1A" or "Cohort 3E," which outline different treatment sequences and combinations rather than specific drug strengths or physical dosage forms. The current data does not specify different dosing regimens for pediatric patients.
Side Effects
The provided data for the safety profile of Lifileucel in the clinical trial (NCT02360579) lists participant counts for various events across different cohorts. However, the specific names of these side effects or adverse events are not included in the data. Therefore, it is not possible to present a list of common side effects, their frequencies, or comparisons to placebo as requested.
Clinical Trial Results
The efficacy of Lifileucel was evaluated in a clinical trial (NCT02360579) involving patients with metastatic melanoma. This study included several cohorts, with results reported for Objective Response Rate (ORR), Duration of Response (DoR), Progression-Free Survival (PFS), and Overall Survival (OS).
Cohort 1 (12 Participants)
- Objective Response Rate (ORR): 4 out of 12 participants (33.3%) experienced an objective response to treatment.
- Progression-Free Survival (PFS): The median time patients lived without their disease getting worse was 2.6 months.
- Overall Survival (OS): The median overall survival for patients in this cohort was 12.9 months.
Cohort 2 (48 Participants)
- Objective Response Rate (ORR): 23 out of 48 participants (47.9%) achieved an objective response.
- Progression-Free Survival (PFS): The median time patients lived without their disease worsening was 4.1 months.
- Overall Survival (OS): The median overall survival for patients in this cohort was 15.6 months.
Cohort 3
- Objective Response Rate (ORR): 1 participant achieved an objective response.
Cohort 4 (72 Participants)
- Objective Response Rate (ORR): 25 out of 72 participants (34.7%) experienced an objective response.
- Duration of Response (DoR): For those who responded, the median duration of their response was 10.4 months.
- Progression-Free Survival (PFS): The median time patients lived without their disease getting worse was 3.9 months.
- Overall Survival (OS): The median overall survival for patients in this cohort was 12.7 months.
Currently Recruiting Trials
Several clinical trials are actively seeking participants to further investigate lifileucel, an innovative cell therapy. These studies aim to evaluate its effectiveness and safety across various advanced cancers, often in individuals who have already received other treatments.
One Phase 2 study, NCT07288203, is enrolling up to 100 adults with previously treated advanced melanoma. This trial focuses on lifileucel (tumor-infiltrating lymphocytes) as a single agent therapy.
Another Phase 2 study, NCT06481592, is investigating the lifileucel regimen in 60 adults with previously treated advanced endometrial cancer. The goal is to assess its efficacy and safety in this patient population.
A larger Phase 3 trial, NCT05727904, is comparing lifileucel in combination with pembrolizumab against pembrolizumab alone. This study is recruiting up to 670 participants with untreated, unresectable, or metastatic melanoma.
For individuals with metastatic uveal melanoma, a Phase 1 open-label study, NCT05607095, is evaluating lifileucel (LN-144). This trial is targeting 30 participants.
Finally, a broad Phase 2 study, NCT03645928, is exploring lifileucel (LN-144/LN-145) as an adoptive cell therapy in 245 patients with various solid tumors, including metastatic melanoma, squamous cell carcinoma of the head and neck, and non-small cell lung cancer.
Where to Participate
Clinical trials for lifileucel are currently being conducted across a wide geographic area, with 88 sites located in 53 cities across 31 states. This extensive network aims to make participation accessible to more individuals.
Some of the top locations with multiple participating sites include:
- Detroit, Michigan
- Los Angeles, California
- New York, New York
- Orlando, Florida
- Nashville, Tennessee
- Louisville, Kentucky
- Columbus, Ohio
- Tampa, Florida
- Philadelphia, Pennsylvania
- Boston, Massachusetts
Eligibility criteria for these studies generally require participants to be adults, specifically between 18 and 70 years of age. All genders are welcome to participate, but healthy volunteers and children are not eligible for these trials.
Development Timeline
The journey of lifileucel began with its first clinical trial initiated on February 10, 2015. Since then, the development program has steadily expanded, with the latest trial projected to conclude in late 2025.
Initially, early investigations explored conditions such as IBS-C and hyperphosphatemia. However, the focus quickly shifted and expanded significantly into oncology, driven primarily by Iovance Biotherapeutics, Inc., which has sponsored five of the trials. Other key contributors include Memorial Sloan Kettering Cancer Center, Immatics US, Inc., Richard Wu, and the University of Kansas Medical Center.
To date, a total of 10 clinical trials have been conducted or are ongoing for lifileucel, enrolling approximately 1,709 participants. These trials span various phases of development, including three Phase 1 studies, five Phase 2 studies, and two Phase 3 studies. The pipeline has broadened to address a range of challenging cancers, including various forms of melanoma (cutaneous, uveal, unresectable, metastatic), non-small cell lung cancer, squamous cell carcinoma of the head and neck, and endometrial cancer, reflecting a comprehensive approach to its therapeutic potential.