Cancer cell therapy for melanoma has potential to save ‘thousands’ of lives each year
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A single dose of lifileucel conferred an objective response in nearly one-third of patients with advanced unresectable or metastatic melanoma, results from the phase 2 C-144-01 trial showed.
Data from the study presented at Society for Immunotherapy of Cancer Annual Meeting suggest the durability for the investigational cell therapy is better than previous treatments used in this patient population, the investigators noted.
Background
Limited treatment options exist for patients with unresectable or metastatic melanoma who experience disease progression after receiving immune checkpoint inhibitors and other targeted therapies, according to Jason A. Chesney, MD, PhD, director of James Graham Brown Cancer Center and associate vice president for health affairs at University of Louisville.
Lifileucel (LN-144, Iovance Biotherapeutics) is a cryopreserved autologous cell therapy comprising tumor-infiltrating lymphocytes (TILs) derived from a resected portion of a patient’s tumor and multiplied in a laboratory.
“The TIL product contains a high concentration of personalized, polyclonal cancer antigen-specific cytotoxic T cells that are capable of killing the patient’s cancer cells and promoting cancer immunity,” Chesney told Healio.
Based on published results across 3 decades suggesting the effectiveness of TIL therapy in patients with advanced melanoma, his group decided to conduct a pooled analysis of two cohorts from the C-144-01 trial to produce the largest phase 2 study of patients to receive adoptive cell therapy for advanced melanoma after disease progression on immune checkpoint inhibitors.
Methodology
Chesney and colleagues combined reported outcomes from 153 patients (median age, 56 years; range, 20-79 years; 54% men) enrolled in cohort 2 (n = 66) and cohort 4 (n = 87) from the study.
Investigators used identical eligibility criteria for both study cohorts. Additionally, patients from both cohorts received the same second-generation TIL product manufactured using an identical process at a central Good Manufacturing Practice (GMP) facility.
The study regimen included preconditioning lymphodepletion followed by a single infusion of lifileucel. Patients then received up to six doses of interleukin-2 to promote TIL activity.
Investigator-assessed objective response rate served as the primary endpoint for the analysis. Secondary endpoints included safety and additional efficacy measurements.
Median follow-up was 36.5 months, with a data cutoff point of July 15, 2022.
Key findings
The pooled data set, including both study cohort, showed an ORR of 31.4% (95% CI, 24.1-39.4) for lifileucel. Reduction in tumor burden occurred in 111 patients (79.3%).
Nine patients (5.9%) had a compete response to therapy. Thirty-nine patients (25.5%) had a partial response, whereas nearly half of patients (46.4%) had stable disease after a single infusion of lifileucel.
Twenty-seven patients (17.6%) had progressive disease after therapy.
Investigators noted that 41.7% of patients who responded to therapy had an ongoing response lasting 24 months or longer as of the data cutoff date.
Median duration of response has not yet been reached.
Further analysis showed median OS of 13.9 months (95% CI, 10.6-17.8) for the pooled analysis, with a 12-month OS rate of 54% (95% CI, 45.6-61.6).
Hematologic treatment-related adverse events occurred in all patients but were consistent with the known safety profile of the regimen used in the study.
The most frequently occurring nonhematologic treatment-related adverse events included chills (75%), pyrexia (51.9%) and febrile neutropenia (41.7%).
Clinical implications
These latest results from the C-144-01 trial are further evidence that the TIL regimen is a safe and highly effective treatment for patients with advanced melanoma who have experienced disease progression while receiving immune checkpoint, BRAF or MEK inhibitors, Chesney said.
Data from the C-144-01 trial study are being used to support a rolling biologics license application with the FDA.
FDA approval of lifileucel for patients with advanced melanoma would have groundbreaking impact on clinical care for the disease, according to Chesney.
“FDA approval would translate into thousands of melanoma patients’ lives being saved each year,” he told Healio.
“To my knowledge, the objective response rate, which appears to be very durable, is the highest that has been observed in patients who have progressed on immune checkpoint inhibitors.”
Perspective
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Darwin Ye
Lifileucel showed meaningful clinical efficacy and a manageable safety profile in a heavily pretreated population of patients.
What explains this additional clinical efficacy provided by lifileucel following immune checkpoint inhibitors? Is it a similar set of tumor-reactive T cells that are acting in lifileucel treatment? Or is it a different set of T cells recognizing a different set of neoantigens that can explain this added response? What if additional cycles of immune checkpoint inhibitors were now applied following lifileucel? These are all important questions in need of further exploration.
A key takeaway from this trial’s results is that we need biomarkers to stratify patients who will have a response to additional immunotherapies following treatment with immune checkpoint inhibitors. In this study, prior anti-CTLA-4 use was associated with a response to lifileucel. Conversely, receiving previous anti-PD-1 plus anti-CTLA-4 combination therapy use seemed linked to nonresponse to lifileucel.
I anticipate upcoming results from similar trials and hope to learn key insights into parameters that may maximize response to therapy, including which immunotherapy combinations are effective, and whether the sequential order of applying immunotherapies impacts outcomes.
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Sarnaik A, et al. Abstract 789. Presented at: Society for Immunotherapy of Cancer Annual Meeting; Nov. 8-12, 2022; Boston.
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