Iovance Reports 59.1% Response Rate With Lifileucel in mNSCLC

Iovance Biotherapeutics reported updated Phase 2 results for lifileucel in previously treated non-squamous metastatic non-small-cell lung cancer (mNSCLC), alongside plans to advance a biomarker-guided tumor-infiltrating lymphocyte (TIL) therapy strategy. In the IOV-LUN-202 study, the overall response rate (ORR) was 24.6% among 69 patients, while a retrospectively identified subgroup defined by KRAS wild-type and HER2 wild-type tumors and a current or former smoking history achieved an ORR of 59.1%. The findings provide a rationale for prospective evaluation of biomarker-based patient selection, although the subgroup results require validation.

Updated Phase 2 Results Show Antitumor Activity

As of the October 14, 2026, data cutoff, 17 of 69 patients treated in Cohorts 1 and 2 had responded to lifileucel. The responses included 15 confirmed responses and two unconfirmed partial responses awaiting confirmation, resulting in an ORR of 24.6%.

The updated response rate was broadly consistent with the previously reported ORR of 25.6% among 39 patients. Participants had experienced disease progression on or after platinum-based chemotherapy and immune checkpoint inhibitor therapy. The expanded analysis included 30 additional patients who had not been prospectively selected using the subsequently identified biomarker criteria.

Iovance reported that response durability and the safety profile remained consistent with previous reports. The company also reported an improved overall safety profile with an updated, reduced-dose lymphodepletion regimen. Independent radiological assessments were ongoing, and the two unconfirmed responses remain subject to confirmation.

Biomarker Analysis Identifies a Potentially Responsive Subgroup

Retrospective analyses identified KRAS status as a potential biomarker associated with response to lifileucel. Among 69 patients, the ORR was 43.3% (13/30) in those with KRAS wild-type tumors, compared with 11.4% (4/35) in patients with KRAS-mutant disease. Both complete responses occurred in the KRAS wild-type subgroup.

Further analysis suggested that combining tumor biomarkers with smoking history could refine patient selection. The ORR increased to 52.0% (13/25) among patients with KRAS wild-type and HER2 wild-type tumors. Among the 22 patients who also had a current or former smoking history, the ORR reached 59.1% (13/22).

This subgroup represented 31.9% of the overall study population but accounted for 76.5% of the observed responses. The concentration of responses suggests a potentially useful patient-selection strategy, but it does not establish that the combined criteria predict treatment benefit. The analysis was retrospective, and prospective validation remains necessary.

The proposed biological rationale involves differences in tumor antigen presentation and the immune microenvironment. Preclinical research suggests that oncogenic KRAS and aberrant HER2 signaling may contribute to immune suppression, while smoking-associated mutations may generate additional tumor targets recognizable by polyclonal TILs. These mechanisms provide a rationale for further investigation but do not independently establish clinical benefit.

POSITILITY to Prospectively Evaluate Biomarker-Guided Treatment

Iovance plans to begin enrollment in November 2026 for POSITILITY, a prospective, biomarker-enriched cohort within the ongoing Phase 2 IOV-LUN-202 trial. Designed with registrational intent, the cohort will evaluate whether the combined biomarker criteria can identify patients more likely to benefit from lifileucel.

Cohorts 1 and 2 are completing enrollment, with approximately 80 patients with non-squamous NSCLC expected in the final dataset. Iovance plans to pursue a supplemental biologics license application (sBLA) for lifileucel in this population in 2027, with discussions with the U.S. Food and Drug Administration ongoing. The timing and regulatory pathway remain subject to further clinical evaluation and FDA discussions.

Frontline Findings Support Further Investigation

A separate analysis of frontline Cohort 3A of IOV-COM-202 found responses in six of seven patients with non-squamous mNSCLC, KRAS wild-type tumors and a current or former smoking history who received lifileucel with pembrolizumab without chemotherapy. The resulting ORR was 85.7%. HER2 status was not assessed, and the small sample limits interpretation.

Iovance plans to initiate OPTILISM in 2027 to evaluate lifileucel in biomarker-enriched frontline non-squamous mNSCLC. Together, OPTILISM and POSITILITY are intended to investigate biomarker-guided patient selection across frontline and second-line settings.

Prospective Validation Will Determine Clinical Relevance

The updated IOV-LUN-202 findings support continued evaluation of lifileucel in previously treated non-squamous mNSCLC. The overall ORR remained broadly consistent as the dataset expanded, while retrospective analyses identified a subgroup with a substantially higher observed response rate.

The key question is whether prospective biomarker-based selection can reproduce this response signal in a defined patient population. POSITILITY will help address that question and inform the potential regulatory pathway. Lifileucel remains investigational for mNSCLC, and the current findings do not establish efficacy in the biomarker-enriched population or confirm a future regulatory outcome.

Reference

Iovance Reports Updated IOV-LUN-202 Results and Adds Precision TIL Strategy for Second-Line Metastatic Non-Small-Cell Lung Cancer (mNSCLC), Iovance Biotherapeutics, 29 October 2026

Autologous LN-145 in Patients with Metastatic Non-Small-Cell Lung Cancer, ClinicalTrials.gov ID NCT04614103