Philadelphia, Pennsylvania — October 29, 2026
Iovance Biotherapeutics, Inc. announced updated results from Cohorts 1 and 2 of its Phase 2 IOV-LUN-202 clinical trial, evaluating lifileucel in patients with previously treated non-squamous metastatic non-small-cell lung cancer (mNSCLC). Among 69 patients whose disease had progressed following platinum-based chemotherapy and immune checkpoint inhibitor therapy, 17 patients responded, representing an objective response rate (ORR) of 24.6%, consistent with the previously reported 25.6% ORR in 39 patients. A retrospective biomarker analysis identified a subgroup defined by KRAS wild-type, HER2 wild-type status and current or former smoking history, in which the ORR reached 59.1% (13 of 22 patients). Based on these findings, Iovance is advancing a precision tumour-infiltrating lymphocyte (TIL) strategy through POSI-TIL-ITY, a prospective biomarker-enriched study within IOV-LUN-202, with enrolment expected to begin in November 2026. The company also plans to pursue a supplemental Biologics License Application (sBLA) for lifileucel in non-squamous mNSCLC in 2027, subject to ongoing discussions with the US Food and Drug Administration (FDA).
Lifileucel Demonstrates Consistent Activity in Updated Phase 2 Results
The updated IOV-LUN-202 dataset included 30 additional patients, bringing the total to 69 participants with previously treated non-squamous mNSCLC who received lifileucel. As of the October 14, 2026 data cutoff, 17 responses were reported, including 15 confirmed responses and two unconfirmed partial responses awaiting confirmation. The overall response rate of 24.6% was consistent with the earlier analysis, supporting the previously observed treatment activity in this population. Response durability and the safety profile also remained consistent with earlier reports. The study incorporates an updated, reduced-dose lymphodepletion regimen, which Iovance said has improved the overall safety profile. Cohorts 1 and 2 are completing enrolment, with approximately 80 patients expected in the final non-squamous dataset. The company plans to use the broader study results to support a potential 2027 sBLA submission. Independent radiologic review is ongoing, and further programme updates are expected in 2027. Lifileucel remains investigational for mNSCLC and has not been approved for this indication.
KRAS and HER2 Biomarkers Identify a Higher-Response Patient Subgroup
A retrospective analysis identified KRAS mutation status as a key factor associated with response to lifileucel. Among 30 patients with KRAS wild-type tumours, the ORR was 43.3% (13 responses), compared with 11.4% (four responses) among 35 patients with KRAS-mutant disease. Both complete responses occurred in the KRAS wild-type subgroup. Further analysis combining KRAS wild-type status with HER2 wild-type status and current or former smoking history identified 22 patients with an ORR of 59.1% (13 of 22). This subgroup represented approximately 31.9% of the broader study population but accounted for 76.5% of observed responses. The analysis also showed an ORR of 52.0% among 25 patients with both KRAS and HER2 wild-type tumours. Iovance’s proposed biological rationale involves tumour antigen presentation and the immune microenvironment: KRAS-related signalling may impair antigen presentation, while smoking-associated mutations may create additional tumour targets for recognition by polyclonal TIL. These findings are retrospective and require prospective validation before the biomarkers can be established as reliable patient-selection criteria.
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POSI-TIL-ITY Advances Precision TIL Development in Lung Cancer
Iovance plans to begin enrolment in POSI-TIL-ITY in November 2026, making it a prospective, biomarker-enriched cohort within the Phase 2 IOV-LUN-202 programme. The study is designed with registrational intent and will evaluate lifileucel in patients selected using the combined biomarker strategy, subject to FDA feedback. The company also reported supporting findings from frontline Cohort 3A of the separate IOV-COM-202 study. In that analysis, six of seven patients with non-squamous mNSCLC, KRAS wild-type tumours and a current or former smoking history responded to lifileucel combined with pembrolizumab without chemotherapy, producing an ORR of 85.7%; HER2 status was not assessed in this group. Iovance plans to initiate OP-TIL-ISM, a biomarker-enriched frontline trial, in 2027. Together, POSI-TIL-ITY and OP-TIL-ISM are intended to investigate precision TIL therapy in second-line and frontline treatment settings. Lifileucel is already approved as Amtagvi for certain previously treated advanced melanoma patients, but its use in mNSCLC remains investigational. The upcoming studies will determine whether biomarker-guided selection can translate the encouraging response signals into confirmatory clinical evidence and support a potential expansion of lifileucel’s therapeutic applications.
Source: Iovance Biotherapeutics ,Press release
