‘There may be a role’ for frontline lifileucel plus pembrolizumab in advanced melanoma
Click Here to Manage Email Alerts
Key takeaways:
- Combining lifileucel plus pembrolizumab conferred a complete response in nearly one-third of patients with unresectable or metastatic melanoma.
- Common adverse events included neutropenia and lymphopenia.
CHICAGO — A front-line treatment regimen including lifileucel and pembrolizumab produced ongoing durable responses in some patients with unresectable or metastatic melanoma, according to findings presented at ASCO Annual Meeting.
Additionally, the treatment regimen did not produce any unexpected toxicities, researchers said.
“A single dose of lifileucel combined with pembrolizumab demonstrated manageable and expected safety profile,” Sajeve Samuel Thomas, MD, an oncologist/hematologist at Orlando Health Cancer Institute, said during his presentation. “The treatment adverse events were consistent with what we expect with underlying disease and the known safety profile of administration of lifileucel, most of it interleukin-2 and lymphodepletion and reversible.”
Background and methodology
Lifileucel (Amtagvi, Iovance Biotherapeutics) became the first cell therapy to utilize tumor-infiltrating lymphocytes (TIL) for solid tumors to gain FDA approval in February.
It garnered an indication for adults with unresectable or metastatic melanoma who had previously been treated with a PD-1 inhibitor and, if BRAF-positive, a BRAF inhibitor with or without a MEK inhibitor.
Immune checkpoint inhibitors had been standard front-line therapy for patients with advanced melanoma, but only 30% to 40% respond to treatment, according to background information Healio previously reported.
“Lifileucel has the potential to improve outcomes over current immune checkpoint inhibitor mono- or combination therapy in the frontline/immune checkpoint inhibitor-naïve setting,” Thomas said.
The multicenter IOV-COM-202 study assessed lifileucel in combination with pembrolizumab (Keytruda, Merck), an anti-PD-1 therapy, in 23 patients (median age, 51 years; 65.2% men; 100% white) who had not been previously treated with an immune checkpoint inhibitor. Study participants could have been previously treated with a BRAF or MEK inhibitor if positive for a BRAF mutation.
Participants also needed to have a lesion at least 1.5 cm in diameter for lifileucel manufacturing, and at least one measurable lesion to evaluate response.
Individuals received pembrolizumab, nonmyeloablative lymphodepletion, a single lifileucel infusion, between 1-6 doses of interleukin-2 and continued pembrolizumab for 2 years or until disease progression or unacceptable toxicity.
Objective response rate and incidence of treatment-emergent adverse events (TEAEs) served as the study’s primary endpoints.
Results and next steps
At a median follow-up of 21.7 months, researchers confirmed an ORR in 65.2%, including complete response in 30.4%. Additionally, 26.1% of patients had stable disease.
They observed an initial response in a median of 2.6 months, which included a pair of patients achieving 100% disease regression by week 6.
Median duration of response had not been reached.
Among responders, 66.7% have an ongoing response, four others discontinued while in response and 53.3% have been progression free for at least 1 year.
“All response-evaluable patients demonstrated regression of target lesions,” Thomas said.
All patients developed grade 3 or 4 neutropenia and lymphopenia and 95.7% developed leukopenia and thrombocytopenia.
“But by day 30, the grade 3, grade 4 hematologic issues resolved to less than a grade 2 in 90% to 95% of the patients [neutropenia, leukopenia, thrombocytopenia and anemia] with the exception of leukopenia,” Thomas said.
Common any-grade nonhematologic TEAEs included chills (82.6%), pyrexia (78.3%), nausea (78.3%) and vomiting (65.2%). The most frequent grade 3 or worse nonhematologic TEAEs included febrile neutropenia (43.5%) and hypertension (21.7%).
“These results serve as rationale for TILVANCE-301, an ongoing registrational, randomized trial assessing lifileucel plus pembrolizumab in frontline advanced melanoma,” Thomas said.
Sunandana Chandra, MD, MS, associate professor in the division of hematology and oncology at Robert H. Lurie Comprehensive Cancer Center at Northwestern University, supported that claim using unpublished data from Stephanie L. Goff, MD, head of clinical operations for surgery branch CGMP facilities at National Cancer Institute, and Steven A. Rosenberg, MD, PhD, senior investigator in NCI’s Center for Cancer Research and chief of the NCI Surgery Branch.
The research indicated between 49% and 55% of patients had response to TIL therapy in the front-line setting, with between 21% and 22% having a complete response.
“I think this data is clear in suggesting that there may be a role for using TIL in the frontline setting in those who are PD-1 refractory,” Chandra said.
Collapse
Thomas SS, et al. Abstract 9505. Presented at: ASCO Annual Meeting 2024; May 31-June 4, 2024: Chicago.
Click Here to Manage Email Alerts