Lifileucel Yields Responses in Metastatic Non–Small Cell Lung Cancer


Phase 2 data support additional investigation of lifileucel as a treatment for patients with metastatic non–small cell lung cancer.

“These results are encouraging and warrant further investigation of lifileucel in patients with [metastatic] NSCLC," according to the study authors.

“These results are encouraging and warrant further investigation of lifileucel in patients with [metastatic] NSCLC," according to the study authors.

Treatment with the autologous tumor-infiltrating lymphocyte (TIL) cell therapy lifileucel (Amtagvi) produced responses in a small cohort of patients with heavily pretreated metastatic non–small cell lung cancer (NSCLC), including those with different mutational burdens and PD-L1 expression, according to findings from the phase 2 IOV-COM-202 study (NCT03645928) published in Cancer Discovery.

After a median follow-up of 16 months (range, 0.1+ to 27.6), lifileucel elicited an objective response rate (ORR) of 21.4% (n = 6/28), which included 1 complete metabolic response and 5 partial responses (PRs). Additionally, 79.2% of patients had reductions in tumor burden following study treatment. The duration of response (DOR) ranged from 1.1+ to 26.2+ months.

Ongoing responses were observed in 1 patient with a complete metabolic response at 26.2+ months and in another with a PR at 8.7+ months; neither patient received subsequent local or systemic treatment. Of 4 patients without a sustained response, 3 had radiographic disease progression, and 1 died following bowel perforation.

One patient with PD-L1–negative disease experienced a complete metabolic response, and another with a PR had a tumor that was PD-L1 negative. The other 4 patients with a response all had PD-L1–positive disease, with tumor proportion scores (TPS) ranging from 5% to 90%.

One patient with a response had a tumor harboring a KRAS G12C point mutation and MET amplification, another responder had KRAS G12D–mutated disease. Additionally, STK11 and KEAP1 mutations appeared in 1 patient with a response, which are believed to typically confer worse outcomes with PD-1/PD-L1 inhibitors.

“In summary, TIL cell therapy represents a feasible, individualized, and polyclonal potential treatment option for patients with [metastatic] NSCLC. This is the first study to demonstrate the efficacy and safety of centrally manufactured autologous TIL cell therapy as a single modality in patients with [metastatic] NSCLC after treatment with anti–PD-1/PD-L1 therapy,” lead study author Adam J. Schoenfeld, MD, a medical oncologist in the Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center, and coauthors wrote. “These results are encouraging and warrant further investigation of lifileucel in patients with [metastatic] NSCLC.”

In the prospective, open-label, multicenter phase 2 trial, patients with various solid tumors were assigned to receive lifileucel alone or in combination with an immune checkpoint inhibitor.In this report, investigators highlighted findings from cohort 3B of the trial, which included patients with metastatic NSCLC previously treated with 1 to 3 prior lines of systemic therapy.

Patients in cohort 3B received cyclophosphamide at 60 mg/kg daily for 2 days plus fludarabine at 25 mg/m2 daily for 5 days. At approximately 24 hours following the final fludarabine dose, patients received lifileucel as a single infusion followed by a maximum of 6 doses of interleukin-2 (IL-2) at 600,000 IU/kg.

The trial’s primary end points were ORR per RECIST v1.1 guidelines and grade 3 or higher treatment-emergent adverse effects (TEAEs). Secondary end points included the complete response rate, DOR, progression-free survival, and overall survival.

Patients 18 years and older with stage III or IV metastatic NSCLC with radiographic progression following 1 or more prior lines of therapy including an immune checkpoint inhibitor or antibodies targeting PD-1 or PD-L1 were eligible for enrollment on the trial. Other eligibility criteria included having at least 1 resectable lesion, an ECOG performance status of 0 or 1, and adequate organ function.

The full analysis set included 28 patients, whose median age was 61 years (range, 40-74). Additionally, most patients had smoked (85.7%), an ECOG performance status of 1 (67.9%), adenocarcinoma histology (78.6%), a PD-L1 TPS of 1% to 49% (39.3%), and stage IVB disease at entry (50.0%). The most common types of prior systemic therapy included immunotherapy (100.0%) followed by chemotherapy (96.4%), monoclonal antibodies (28.6%), and targeted therapies (7.1%). Common resected tumor sites included the lung (60.7%), lymph node (10.7%), and liver (7.1%).

The median time from tumor resection to lifileucel administration was 35.5 days (range, 28-112), and patients received a median of 20.9 x 109 (range, 1.4 x 109 to 53.2 x 109) TIL cells. Any-grade TEAEs affected 100.0% of patients and included chills (67.9%), hypotension (64.3%), pyrexia (57.1%), and hypoxia (53.6%). Additionally, grade 3 or higher TEAEs occurred in 96.4% of patients, with the most common including febrile neutropenia (28.6%), hypertension (21.4%), and hypoxia (17.9%). Two patients died due to TEAEs, including one who had cardiac failure and another due to multiple organ failure.

Grade 3/4 hematologic laboratory abnormalities included low leukocytes (100.0%), lymphocytes (100.0%), neutrophils (100.0%), platelets (96.4%), and hemoglobin (67.9%).


Schoenfeld AJ, Lee SM, de Spéville BD, et al. Lifileucel, an autologous tumor-infiltrating lymphocyte monotherapy, in patients with advanced non-small cell lung cancer resistant to immune checkpoint inhibitors. Cancer Discovery. Published online April 2, 2024. doi:10.1158/2159-8290.CD-23-1334

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