Lifileucel Shows 50% Response Rate in Refractory UPS and Liposarcoma

Lifileucel (Amtagvi; Iovance Biotherapeutics), an autologous tumor-infiltrating lymphocyte (TIL) therapy, produced confirmed partial responses in 4 of 8 patients with refractory metastatic undifferentiated pleomorphic sarcoma (UPS) or dedifferentiated liposarcoma (DDLS), according to pilot trial data presented at the European Society for Medical Oncology Congress 2026 in Madrid, Spain.¹ All 4 responses were ongoing at the September 9, 2026, data cutoff, and the trial met its primary feasibility end point.

Among all 10 infused patients, the objective response rate (ORR) was 40% (95% CI, 12.2%-73.8%), and the disease control rate was 80% (95% CI, 44.4%-97.5%).

Unmet Needs Persist in UPS and Dedifferentiated Liposarcoma

Refractory metastatic UPS and DDLS have limited effective treatment options, the authors noted. In the French METASARC observational study of patients with metastatic soft tissue sarcoma, median overall survival from the start of first-line systemic therapy was 11 months for UPS and 11.8 months for DDLS.²

The FDA granted lifileucel accelerated approval in February 2024 for previously treated unresectable or metastatic melanoma, based on an ORR of 31.5% in the phase 2 C-144-01 trial.³ Because TILs are present in both UPS and DDLS, the authors wrote, the histologies are reasonable candidates for the therapy.¹ Iovance first reported a 50% confirmed ORR among the first 6 evaluable patients in February 2026.⁴

The investigator-initiated pilot trial (NCT05607095), led by Memorial Sloan Kettering Cancer Center, enrolled patients with unresectable or metastatic UPS or DDLS after at least 1 prior systemic therapy who had a lesion of at least 1.5 cm for TIL harvest and an Eastern Cooperative Oncology Group performance status of 0 or 1. After tumor harvest and roughly 22 days of manufacturing, patients received lymphodepleting cyclophosphamide (60 mg/kg for 2 doses) and fludarabine (25 mg/m² for 5 doses), a single lifileucel infusion, and up to 6 doses of interleukin 2 (600,000 IU/kg).

Primary end points were feasibility, defined as at least 6 of 10 patients infused, and the rate of grade 3 or higher treatment-related adverse events. Secondary end points included ORR by RECIST 1.1, disease control rate, and duration of response. Twelve patients (8 with DDLS, 4 with UPS) underwent TIL harvest. Their median age was 59 years (IQR, 49.5-64), 8 were men, and half had received 2 prior lines of therapy (range, 1-7).

Lifileucel Response Rates in Refractory UPS and DDLS

Ten of 12 patients (83.3%; 95% CI, 51.6%-97.9%) received lifileucel, meeting the feasibility end point. One patient was not infused because of a manufacturing failure and another because of clinical progression. Eight infused patients received product that met manufacturing specifications.

Among those 8 patients, 4 had confirmed partial responses (ORR, 50.0%; 95% CI, 15.7%-84.3%), 2 with UPS, and 2 with DDLS. Responses were ongoing at 6, 26, 40, and 46 weeks, and the median duration of response was not reached. Two responders had previously received a checkpoint inhibitor. Both patients who received out-of-specification products had stable disease.

“All [partial responses] are confirmed and ongoing, providing preliminary evidence of activity and supporting further evaluation,” the authors wrote in the abstract.

All 10 infused patients had grade 4 cytopenias, which the investigators described as expected with the conditioning chemotherapy, and 8 had grade 3 or higher nonhematologic treatment-related adverse events, most often febrile neutropenia (40%). No grade 5 events were treatment related. One patient had a grade 4 pulmonary infection and hemorrhage after TIL harvest, and 1 died of disease after progression.

The findings are limited by the small, single-arm design with no comparator and wide CIs around the response rates. Follow-up remains short for some responders, and the data have not been published in a peer-reviewed journal. The trial was supported by Iovance, and presenter Lauren Banks, MD, PhD, a sarcoma medical oncologist at Memorial Sloan Kettering, disclosed that she chairs the steering committee of the company’s registrational phase 2 SARATOGA trial (NCT07741877).

SARATOGA is enrolling patients with advanced UPS or DDLS refractory to at least 1 prior line of anthracycline-based chemotherapy, with ORR by an independent review committee as the primary end point. The FDA granted lifileucel fast track designation in advanced UPS and DDLS in the second quarter of 2026, according to Iovance.⁵ An analysis of 10 additional pilot patients and a pilot angiosarcoma cohort are under way.¹

“This level of durability provides meaningful time for patients with refractory UPS and [DDLS] suffering from high disease burden, poor quality of life, and a lack of effective treatments, including no approved immunotherapy options,” Banks said in a statement.⁶

References

1. Banks L, Bartlett E, Deng Y, et al. Lifileucel in patients with undifferentiated pleomorphic sarcoma (UPS) or dedifferentiated liposarcoma (DDLS). Paper presented at: European Society for Medical Oncology Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract 3725RO.

2. Savina M, Le Cesne A, Blay JY, et al. Patterns of care and outcomes of patients with METAstatic soft tissue SARComa in a real-life setting: the METASARC observational study. BMC Med. 2017;15(1):78. doi:10.1186/s12916-017-0831-7

3. FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. FDA. February 16, 2024. Accessed October 27, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lifileucel-unresectable-or-metastatic-melanoma

4. Iovance announces positive results from the first clinical trial for TIL cell therapy in soft tissue sarcomas. News release. Iovance Biotherapeutics. February 24, 2026. Accessed October 27, 2026. https://ir.iovance.com/node/15606/pdf

5. Iovance announces data showing durable responses with lifileucel TIL cell therapy in advanced soft tissue sarcomas at ESMO 2026. News release. Iovance Biotherapeutics. October 26, 2026. Accessed October 27, 2026. https://ir.iovance.com/news-releases/news-release-details/iovance-announces-data-showing-durable-responses-lifileucel-til