Tumor-infiltrating lymphocyte cell therapy ‘potentially viable’ option for advanced NSCLC
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Nearly a quarter of patients with heavily pretreated non-small cell lung cancer achieved an objective response to an infusion of LN-145, according to study results presented at Society for the Immunotherapy of Cancer Annual Meeting.
Early results from the phase 2 trial of the investigational tumor-infiltrating lymphocyte (TIL) cell therapy also showed a disease control rate of 65%.
LN-145 (Iovance Biotherapeutics) is an adoptive cell therapy derived by isolating TILs from a resected portion of a patient’s tumor and multiplying them in a laboratory for subsequent reinfusion into the patient.
“Most patients with advanced non-small cell lung cancer who are treated with first-line immune checkpoint inhibitors — with our without chemotherapy — develop disease progression,” Adam J. Schoenfeld, MD, medical oncologist and lung cancer specialist at Memorial Sloan Kettering Cancer Center, said during a presentation.
“In this setting,” he added, “options that provide deep and durable responses are urgently needed.”
Schoenfeld presented the first safety and efficacy results from cohort 3B of the multicenter phase 2 IOV-COM-202 trial, designed to evaluate autologous TILs for patients with solid tumors.
“This single-finding study demonstrated the feasibility of tumor harvest, TIL manufacturing and TIL treatment in patients with advanced non-small cell lung cancer,” Schoenfeld said. “TIL cell therapy is a potentially viable treatment option for patients with advanced non-small cell lung cancer.”
The cohort included 28 patients (median age, 61 years; range, 40-74; 50% male) with advanced or metastatic NSCLC who received LN-145 monotherapy. Patients received a median two prior lines of therapy, and all patients had received prior treatment with an immune checkpoint inhibitor. The majority (85.7%) were current or former smokers.
Patients underwent nonmyeloablative lymphodepletion with cyclophosphamide and fludarabine prior to IV infusion of LN-145. Patients then received up to six doses of 600,000 IU/kg interleukin-2 to promote TIL activity.
Most TILs (61.7%) were harvested from lung metastases.
Investigator-assessed objective response rate and grade 3 or greater treatment-related adverse events served as the study’s primary endpoints.
Median follow-up was 9.8 months, with a data cutoff date of Aug. 24.
“Initial responses to therapy were early and deepened over time in several patients,” Schoenfeld said. “Despite multiple lines of prior therapy, six patients experienced responses — including two with durable responses.”
TIL therapy conferred a 21% ORR for the entire treatment cohort, with a partial response rate of 17.9%.
One patient (3.6%) achieved a complete metabolic response to therapy that remained ongoing at 20.7 months after infusion.
Researchers reported a 64% disease control rate, and 42.9% of patients had stable disease after infusion.
All patients experienced at least one treatment-related adverse event. Twenty-seven patients (96.4%) of patients experienced a grade 3 or 4 adverse event, the most frequent of which were thrombocytopenia (67.9%), anemia (50%) and hypotension (25%).
"The adverse event profile was manageable and was consistent with the underlying advanced disease and known safety profiles of the nonmyeloablative lymphodepletion and IL-2,” Schoenfeld said. “Most adverse events occurred prior to or within the first 2 weeks after TIL infusion.”
Two patients in the cohort died. One died of cardiac failure related to TIL function, and another died of multiple organ dysfunction syndrome that was possibly related to TIL activity.
“One-time LN-145 treatment with preconditioning ... was well-tolerated,” Schoenfeld said. “Learning from this study will directly inform patient inclusion criteria in the ongoing IOV-LUN-202 study, [which will] include those with fewer lines of prior therapy. [This] may maximize the potential for more sustained responses.”
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Schoenfeld AJ, et al. Abstract 458. Presented at: Society for Immunotherapy of Cancer Annual Meeting; Nov. 10-14, 2021; Washington, D.C.
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