A single infusion of the investigational agent lifileucel—an immunotherapy using cryopreserved autologous tumor-infiltrating lymphocytes (TIL)—induced responses in more than 33% of patients with advanced melanoma whose disease progressed with multiple previous therapies, including PD-1 and BRAF/MEK inhibitors.
These updated results of a phase 2 global multicohort study were reported at the ASCO 2020 virtual annual meeting. The results showed a reduction in tumor burden in 81% of evaluable patients who received TIL therapy with lifileucel in the open-label trial. The response data indicate that “lifileucel therapy can result in responses for those who have metastatic melanoma that is primarily refractory to PD-1 antibody therapy,” said lead investigator Amod Sarnaik, MD, Surgical Oncologist, Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Tampa, FL.
There are currently no effective approved agents for the treatment of advanced metastatic melanoma that progresses after immune checkpoint inhibition and BRAF/MEK inhibition in patients whose tumors have activating mutations in the BRAF proto-oncogene.
The study population consisted of patients with unresectable or metastatic melanoma whose disease had progressed after treatment with at least 1 systemic therapy, including a PD-1 inhibitor and, if BRAF V600 mutation–positive, a BRAF inhibitor or a BRAF/MEK inhibitor. The data presented at the meeting were from cohort 2 of the study, in which 66 patients received cryopreserved TIL therapy with lifileucel.
The patients in cohort 2 were heavily pretreated, with high baseline disease burden (106 mm mean sum of diameters of target lesions), whose disease progressed after a mean of 3.3 previous therapies, including 100% of the patients who had received a PD-1 inhibitor and 80% of those who had received anti–CTLA-4 therapy. Of the 17 patients whose tumors had BRAF V600 mutations, 15 had previously received a BRAF/MEK inhibitor therapy. In all, 77% of the patients had >3 target or nontarget lesions at baseline (mean, 6 lesions), and 42% had baseline liver and/or brain metastases.
The objective response rate (ORR) with TIL therapy in cohort 2 was 36.4%, with 2 (3%) complete responses and 22 (33.3%) partial responses. An additional 43.9% of the patients had stable disease as their best response. A total of 4 patients who were not evaluable were included as nonresponders.
After a median follow-up of 18.7 months, the median duration of response to lifileucel was still not reached. Responses were seen regardless of the location of the tumor resected.
Durable responses were demonstrated across a wide age-range of patients with metastatic melanoma, including those whose disease progressed after receiving anti–CTLA-4 and BRAF-targeted treatments, regardless of BRAF mutation status, and equally in patients with high or low PD-L1 expression.
Compared with the overall cohort, patients with a baseline lactate dehydrogenase level of ≥2 times the upper limit of normal had a trend toward a lower response rate (ORR, 12.5%), as well as patients with a sum of diameters of target lesions at baseline of ≥70 mm (ORR, 25%). These trends, however, were not significant. Responses were observed in patients with bulky disease or with liver and/or brain lesions at baseline.
“Overall, these data indicate that responses from lifileucel therapy are achievable for subjects across a relatively broad range of clinical and pathologic features,” said Dr Sarnaik.
The responses deepened over time, he noted, and 16 responses extended beyond 1 year. In all, 79% of responders had received previous therapy with ipilimumab (Yervoy).
The adverse-event profile with lifileucel therapy was consistent with the underlying advanced disease, lymphodepletion, and interleukin-2 regimens.
“In general, the adverse events were typically expected for a treatment regimen that includes nonmyeloablative lymphodepleting chemotherapy and infusional bolus interleukin-2,” said Dr Sarnaik.
These events included grade 3 or 4 thrombocytopenia in 81.8% of patients, grade 3 or 4 anemia in 56.1%, and grade 3 or 4 febrile neutropenia in 54.5% of patients. The peak onset of toxicities tended to occur relatively soon after TIL infusion, “with a paucity of new adverse events that start beyond 14 days of TIL infusion,” he added.