Lifileucel Demonstrates 50% ORR in Advanced Soft Tissue Sarcomas

Lifileucel (Amtagvi), an autologous tumor-infiltrating lymphocyte (TIL) therapy, demonstrated high response rates in patients with advanced undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS), according to findings from a pilot trial led by Memorial Sloan Kettering Cancer Center (MSKCC).¹

In the first 6 evaluable patients treated with TILs, the investigator-assessed confirmed overall response rate was 50% with a favorable safety profile, suggesting a potential new treatment approach for a patient population that has historically exhausted effective systemic options.

“Patients with UPS and DDLPS suffer from high disease burden, poor quality of life, and a lack of effective treatments, including no approved immunotherapy options,” Lauren Baker Banks, MD, PhD, sarcoma medical oncologist at MSKCC, stated in a news release. “In the second-line setting,[median progression-free survival; mPFS] for many patients is only a few months with [median overall survival; mOS] less than a year.”

Addressing a Critical Void in Sarcoma Care

Advanced UPS and DDLPS represent aggressive high-grade malignancies with a combined annual incidence of over 8,000 patients across the United States and Europe. For patients who progress on frontline chemotherapy, the prognosis remains dismal. Current second-line standards of care typically yield objective response rates of less than 5%, with mPFS of only approximately 2 to 3 months and mOS of 9 to 10 months.^2-4

Lifileucel is approved for use in patients with advanced melanoma with recurrent disease after standard-of-care immunotherapy and targeted therapy options.⁵ It is also under investigation in non–small cell lung cancer (NSCLC) and other malignancies.⁶ TILs are removed from a lesion of adequate size by surgical excision and undergo ex vivo expansion before being given as a one-time infusion along with nonmyeloablative lymphodepleting chemotherapy using cyclophosphamide and fludarabine and high-dose IL-2.

Early Clinical Efficacy Seen

In the open-label phase 1 study (NCT05607095), all enrolled patients had advanced disease with significant disease burden of a mean sum of diameters of 117 mm at baseline.⁷ They were refractory to prior therapy and had received a mean of more than 2 prior lines of therapy. Patients must have had at least 1 tumor lesion or aggregate of lesions of at least 1.5 cm, and adequate blood counts and organ function.

The responses were reported to be deep and improved over time, consistent with lifileucel’s efficacy in melanoma, NSCLC, and other solid tumors.¹ “In the first clinical trial of a TIL cell therapy in UPS and DDLPS, one-time treatment with lifileucel demonstrated compelling and unprecedented response rates with the potential to address a significant unmet need in patients who are refractory to frontline standard of care,” stated Baker Banks.

Regulatory Path and Future Directions

Baker Banks stated that the investigators look forward to presenting the full results from this cohort at a medical conference in 2026.

Following these results, Iovance Biotherapeutics has announced plans to initiate a single-arm registrational trial in second-line advanced UPS and DDLPS in the second quarter of 2026. The company intends to engage with the FDA to discuss an accelerated approval pathway. The company also stated its plans to expand its clinical development program to include other high-grade soft tissue sarcoma subtypes with high unmet needs.

REFERENCES

1. Iovance announces positive results from the first clinical trial for TIL cell therapy in soft tissue sarcomas. News release. Iovance Biotherapeutics, Inc. February 24, 2026. Accessed February 25, 2026. https://tinyurl.com/kevwhuy4

2. Parikh RC, Ingham M, Schommer RT, et al. Treatment patterns and survival among older adults in the United States with advanced soft-tissue sarcomas. Cancer. 2018;124(15):3193-3201. doi:10.1002/cncr.31558

3. Italiano A, Courccex G, Itani Y, et al. Advanced well-differentiated/dedifferentiated liposarcomas: role of chemotherapy and survival. Ann Oncol. 2012;23(6):1602-1607. doi:10.1093/annonc/mdr484

4. Jones RL, Blay JY, Chawla SP, et al. Efficacy and safety findings from MANTRA: A global, randomized, multicenter, phase III study of the MDM2 inhibitor milademetan vs trabectedin in patients with dedifferentiated liposarcomas. Ann Oncol. 2023;34(11):1033-1043. doi:10.1016/j.annonc.2023.08.010

5. FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. FDA. February 16, 2024. Accessed November 14, 2025. https://tinyurl.com/2n4j4eyw

6. Kaur SD, Abubakar MD, Bedi N, et al. Current perspectives on lifileucel tumor-infiltrating lymphocyte therapy: A paradigm shift in immunotherapy. Curr Probl Cancer. 2025. 59;101252. doi:10.1016/j.currproblcancer.2025.101252

7. A study of LN-144 or LN-145 in people with advanced uveal melanoma, undifferentiated pleomorphic sarcoma, or dedifferentiated liposarcoma. ClinicalTrials.gov. Updated February 4, 2026. Accessed February 25, 2026. https://clinicaltrials.gov/study/NCT05607095