Tumor-infiltrating lymphocytes show ‘remarkable’ results in advanced melanoma
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Lifileucel induced high response rates among patients with advanced melanoma whose disease progressed on immune checkpoint and BRAF/MEK inhibitors, according to study results presented during the ASCO20 Virtual Scientific Program.
The cell-based therapy also had an acceptable safety profile, results of the phase 2 study showed.
Lifileucel (LN-144, Iovance Biotherapeutics) is an investigational adoptive cell therapy that uses genetically engineered autologous tumor-infiltrating lymphocytes (TILs) to treat patients with advanced melanoma that progressed despite multiple previous therapies.
“One of the areas of unmet clinical need in metastatic melanoma is what to do with patients after progression on PD-1 antibody systemic therapy,” Amod Sarnaik, MD, surgical oncologist in the department of cutaneous oncology within the immunology program and the Melanoma Center of Excellence at Moffitt Cancer Center, as well as associate professor of oncology and surgery at University of South Florida, told Healio.
“For the longest time, the dogma in the field is that all melanomas either respond to immunotherapy or they don’t,” he added. “So far, subsequent lines of immunotherapy have not proved to be useful.”
This trial is unique in that his group harvested the resident immune cells from within the tumor and expanded those cells in great number ex vivo as a treatment, Sarnaik said.
Sarnaik and colleagues presented data from cohort 2 of the open-label C-144-01 trial.
The trial included patients with unresectable or metastatic melanoma whose disease progressed on at least one previous anti-PD-1 therapy. Patients with BRAF V600-mutant disease had progressed on BRAF or BRAF/MEK inhibitor therapy.
Cohort 2 included 66 patients (median age, 55 years; range, 20-79; 59% men) who received a mean 3.3 (range, 1-9) prior therapies, including anti-PD-1 therapy (100%), anti-CTLA-4 therapy (80%) and BRAF/MEK inhibitors (20%).
Lifileucel cell therapy takes approximately 22 days to manufacture after surgical resection of a tumor lesion to process for the TIL product. Patients received lymphodepletion with cyclophosphamide and fludarabine prior to the one-time lifileucel infusion, followed by up to six doses of IV interleukin-2 agents to enhance treatment efficacy.
Mean number of TIL cells infused was 27.3 × 109.
Investigator-assessed objective response rate according to RECIST version 1.1 served as the study’s primary endpoint. Secondary endpoints included safety and efficacy.
Data cutoff was April 23. Median follow-up was 18.7 months.
The efficacy analysis showed an ORR of 36.4%, including two complete responses (3%) and 22 partial responses (33.3%). Twenty-nine patients (43.9%) had stable disease, for a disease control rate of 80.3%. Eighty-one percent of evaluable patients had a reduction in tumor burden after TIL treatment.
Responses appeared to be durable. Median duration of response was not yet reached, with a range of 2.2 months to beyond 26.9 months.
The response rate in this analysis is “significantly higher than the historical response rate” of between 10% and 20% with standard treatment for patients with advanced melanoma who progressed on immune checkpoint inhibitors, Sarnaik said.
“These results definitely far exceed the standard-of-care treatment,” Sarnaik told Healio. “The results are extremely clinically meaningful.”
The safety analysis showed all patients reported at least one treatment-related adverse event, including 97% with at least one grade 3 or higher adverse event.
The most common grade 3 or higher adverse events included thrombocytopenia (81.8%), anemia (56.1%) and febrile neutropenia (54.5%).
Two patients died during the study, one due to intra-abdominal hemorrhage that may have been related to TIL therapy and another due to acute respiratory failure unrelated to therapy.
Although TIL therapy is associated with considerable toxicities, it differs from CAR-T cell therapy in that symptoms usually manifest within the first few days of treatment, Sarnaik said.
“The good news about the safety profile is that most of the toxicities appear to be reversible within a matter of a few weeks, and after that initial peak in toxicity 2 weeks after the treatment, there are very few adverse events reported,” he told Healio.
Sarnaik said it is important to note that most of the patients in this study had a high burden of disease (106 mm mean target lesion sum of diameters), with progression of disease being their best objective response to previous therapy with an immune checkpoint inhibitor.
“This trial represents a constellation of patients who are treatment refractory with a high burden of disease, so I think the results are remarkable in that context,” Sarnaik said.
For more information:
Amod Sarnaik, MD, can be reached at amod.sarnaik@moffitt.org.
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