Iovance’s Lifileucel Reaches 52% Response Rate in Biomarker-Selected Lung Cancer Subgroup

Iovance Biotherapeutics has reported updated results from its phase 2 IOV-LUN-202 trial of lifileucel, an autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in previously treated non-squamous metastatic non-small cell lung cancer (mNSCLC). On October 29, 2026, the company also announced a biomarker-enriched development strategy for the indication.¹

“These findings are reshaping how we develop TIL therapy for mNSCLC,” said Frederick Vogt, PhD, JD, interim president and chief executive officer of Iovance.¹

How does lifileucel work?

Lifileucel is made from T cells collected from a portion of a patient’s tumor and expanded.² In the manufacturing process described in the NSCLC literature, resected tumor fragments are shipped to a centralized GMP facility, where TILs are expanded over 22 days with interleukin-2 (IL-2) and then cryopreserved.³ Patients receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, a single lifileucel infusion, and up to six doses of high-dose IL-2.³

FDA granted lifileucel accelerated approval as Amtagvi in February 2024 for adults with unresectable or metastatic melanoma previously treated with other therapies.² It remains investigational in NSCLC.¹

In a BioPharm International® video interview on tumor-infiltrating lymphocytes, Jason Bock, PhD, founder and chief executive officer of CTMC, described one of the modality’s advantages. “Another really exciting aspect about TILs is that they have inherent specificity for the tumor,” Bock said.

What did earlier lung cancer data show?

Lifileucel monotherapy was previously evaluated in cohort 3B of the phase 2 IOV-COM-202 trial, which enrolled 28 patients with mNSCLC whose disease had progressed after anti-PD-1 or PD-L1 therapy.³ The objective response rate (ORR) was 21.4%, including one complete metabolic response and five partial responses.³ Two patients died of treatment-emergent adverse events. One death, from multiple organ failure, was assessed as possibly related to lifileucel, with sepsis as an alternative cause.³

What did the updated IOV-LUN-202 data show?

At the October 14, 2026, data cutoff, IOV-LUN-202 Cohorts 1 and 2 included 69 patients with non-squamous mNSCLC whose disease had progressed after platinum-based chemotherapy and immune checkpoint inhibitor therapy.¹ Patients were not selected by biomarker, and ORR was 24.6% (17 of 69), including 2 unconfirmed partial responses.¹

Responses clustered in specific molecular subgroups.¹ ORR was 43.3% with KRAS wild-type tumors and 11.4% with KRAS-mutant tumors, and it reached 52.0% (13 of 25) in tumors wild-type for both KRAS and HER2.¹ In a retrospective subgroup that also required a current or former smoking history, ORR was 59.1% (13 of 22).¹ “In the enriched subgroup, nearly six in ten patients responded, including two complete responses,” Vogt said.¹

Iovance said durability and safety were consistent with prior reports, and that a reduced-dose lymphodepletion regimen improved the safety profile. The release did not report duration-of-response figures or adverse event rates.¹

What is the precision TIL strategy?

Iovance plans to enroll POSITILITY, a prospective, biomarker-enriched cohort within IOV-LUN-202 that the company said is designed with registrational intent, beginning in November 2026.¹ It also plans a frontline trial, OPTILISM, in biomarker-enriched non-squamous mNSCLC starting in 2027.¹ Iovance estimates the enriched population represents about 45% of non-squamous mNSCLC cases diagnosed each year in the US.¹

NSCLC accounts for about 77% of lung cancers. The American Cancer Society estimates about 229,410 new lung cancer cases and 124,990 deaths in the US in 2026.⁴

What happens next?

Iovance plans to submit a supplemental BLA in non-squamous mNSCLC in 2027, with about 80 patients expected in the final dataset.¹ The enriched-subgroup findings come from a retrospective analysis of small patient numbers, and independent review of the responses is ongoing.¹

References

1. Iovance Biotherapeutics. Iovance Reports Updated IOV-LUN-202 Results and Adds Precision TIL Strategy for Second-Line Metastatic Non-Small-Cell Lung Cancer (mNSCLC). Press release. Published October 29, 2026. Accessed October 29, 2026.
2. PharmTech. FDA Approves Amtagvi, First Cell Therapy for Skin Cancer. Published February 20, 2024. Accessed October 29, 2026.
3. Schoenfeld AJ, Lee SM, Doger de Speville B, et al. Lifileucel, an autologous tumor-infiltrating lymphocyte monotherapy, in patients with advanced non–small cell lung cancer resistant to immune checkpoint inhibitors. Cancer Discov. 2024;14(8):1389.
4. American Cancer Society. Key Statistics for Lung Cancer. Accessed October 2026.