Abstract
Preliminary data suggest that a tumor-infiltrating lymphocyte therapy called LN-145 may provide an option for patients with non–small cell lung cancer whose disease has progressed despite receiving other therapies, including PD-1 or PD-L1checkpoint inhibitors. Trial participants had an overall response rate of 21.4%, and the median duration of response had not been reached after 8.2 months of follow-up.
Preliminary data suggest that the tumor-infiltrating lymphocyte (TIL) therapy LN-145 could benefit patients with non–small cell lung cancer (NSCLC) whose disease has progressed despite previous treatments. San Carlos, CA–based Iovance Biotherapeutics, which manufactures LN-145, announced the findings at the end of June.
TILs are isolated from a patient's surgically removed tumor, expanded in the lab, and reinfused without any genetic modifications. Unlike chimeric antigen receptor T cells, which are engineered to target a certain antigen, TILs are polyclonal and recognize a range of tumor antigens.
An infusion of the cells contains “tens of thousands of specificities,” says Friedrich Finckenstein, MD, Iovance's chief medical officer, and that diversity may help TILs battle heterogeneous tumors such as NSCLC. No TIL treatments have received FDA approval, but two previous phase II trials, one of which tested LN-145, reported positive results in melanoma and cervical cancer (Cancer Discov 2019; 9:990). A trial involving patients with NSCLC, which combined the cells with the PD-1 inhibitor nivolumab (Opdivo; Bristol Myers Squibb), also reported early signs of effectiveness (Cancer Discov 2020;10:OF5).
The new data announced by the company come from cohort 3B of the IOV-COM-202 phase II basket trial testing LN-145 in patients with melanoma, head and neck cancer, or NSCLC. The patients in this cohort had advanced or metastatic NSCLC that progressed on previous therapies. All 28 patients whose data were released had previously received PD-1 or PD-L1 checkpoint inhibitors.
The overall response rate of 21.4% included one complete response and five partial responses. Twelve more patients had stable disease. After a median of 8.2 months of follow-up, the median duration of response had not been reached.
For patients like those in the trial, single-agent chemotherapy is standard of care, but Finckenstein says that the response rate for TILs is higher. “This result is meaningful,” he says.
Adam Schoenfeld, MD, of Memorial Sloan Kettering Cancer Center in New York, NY, one of the study's researchers, points to the durability of the response, calling it a major reason that “this is an exciting therapy to pursue.” Schoenfeld also notes that two patients whose tumors shrank were PD-L1–negative, an encouraging finding because such patients typically respond poorly to PD-1 or PD-L1 checkpoint inhibitors.
Before receiving TILs, patients undergo chemotherapy to destroy lymphocytes that might suppress the cells. After the infusion, patients receive up to six doses of IL2 to stimulate the restored cells, which infiltrate and attack the tumor. Side effects such as fever, nausea, and cytopenia can result. Finckenstein says that trial participants did not suffer any unexpected adverse effects. However, Iovance did not specify the types or frequencies of side effects.
“These are the most promising results for any adoptive T-cell approach for NSCLC,” says John Heymach, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, who was not connected to the trial. As the trial progresses, Heymach will be watching for data on response duration and progression-free survival, which will reveal whether patients whose tumors don't shrink still benefit from the treatment.
“While there is activity, it is modest,” says Justin Gainor, MD, of Massachusetts General Cancer Center in Boston, who also was not connected to the trial. “We need more information to sort out which patients are most likely to respond to an agent like this.”
Additional research may help resolve how effective the TILs are. Two other arms of the IOV-COM-202 trial include patients with NSCLC, and a separate Iovance-sponsored phase II trial is testing LN-145 as a second-line therapy in patients with the disease. –Mitch Leslie