Iovance Biotherapeutics reported updated results on October 29 from Cohorts 1 and 2 of its Phase 2 IOV-LUN-202 trial of lifileucel, its tumor infiltrating lymphocyte therapy, in patients with non squamous metastatic non small cell lung cancer whose disease had progressed after platinum chemotherapy and immune checkpoint inhibition. In 69 patients enrolled without prospective biomarker selection, 17 responded, an objective response rate of 24.6 percent, consistent with the 25.6 percent previously reported in 39 patients. The cohort is completing enrollment, with about 80 patients expected in the final dataset, and the company plans a supplemental Biologics License Application for lifileucel in this population in 2027, with Food and Drug Administration discussions ongoing.
The headline inside the release is a subgroup found retrospectively. Patients whose tumors were KRAS wild type responded at 43.3 percent, 13 of 30, against 11.4 percent, 4 of 35, in KRAS mutant disease, and both complete responses were in KRAS wild type tumors. Adding HER2 wild type status and current or former smoking narrowed the group to 22 patients, under a third of the study population, who accounted for 13 of the 17 responses, a response rate of 59.1 percent. The company offered a biological rationale: published preclinical work links oncogenic KRAS signalling to impaired antigen presentation and immune suppression, which would blunt a therapy that depends on tumor cells displaying targets to infused lymphocytes.
Iovance is converting that retrospective finding into a prospective test. A new cohort within the trial, called POSITILITY, is described as a first in class biomarker enriched study with registrational intent, and begins enrollment in November 2026, selecting patients on the combined KRAS wild type, HER2 wild type and smoking history criteria. The company also said response durability and safety remained consistent with earlier reports, and that an updated, reduced dose lymphodepletion regimen has improved the safety profile.
The discipline point is the order of operations. A 59.1 percent response rate in a subgroup chosen because it responded is evidence for a hypothesis, not evidence the hypothesis is true, and the trial that can prove it is the one starting in November, not the one just reported. For the 2027 application, the broader population figure, 24.6 percent in a setting with few options, is the number regulators will weigh first. Iovance reports its third quarter results on November 5, when the commercial performance of lifileucel in its approved melanoma use will sit next to this lung expansion case.