TIL Adoptive Cell Therapy for the Treatment of mNSC Lung Cancer

Article

A new TIL therapy seeks to improve on current treatments for metastatic non-small cell lung cancer such as PD-1 inhibitors.

This content originally appeared on our sister site, Targeted Oncology.

A recent study published in Nature evaluated a new cell therapy containing autologous tumor-infiltrating lymphocytes (TILs) followed by nivolumab (Opdivo) maintenance and found it to be both safe and clinically active in patients with metastatic non-small cell lung cancer (NSCLC).

Most patients will progress within 12 months with PD-1 inhibitors even when combined with platinum-doublet chemotherapy and the majority of patients treated with PD-1 inhibitors will not have an objective response.

While immunotherapy has shown promise, progress is incremental. The use of adoptive cell therapy (ACT), which uses TILs from the patients cultured tumor has prompted a durable complete remission in certain subsets of patients with metastatic melanoma. The strategy has also been studied in cholangiocarcinoma, cervical cancer, colorectal cancer, and breast cancer.

The current phase 1 study is the first time it has been looked at in NSCLC. The study has an actual enrollment of 20 participants with an estimated completion date of December 2023. The primary end point is dose-limiting toxicities. The secondary end point is objective response rate.2

During the study, all patients received TIL in combination with nivolumab.

Of the 20 patients accrued, 50% were current or former smokers. The median age of participants was 54 years old (range, 38-75) with a median PD-L1 proportion score of 6%. Forty percent of patients had a PD-L1 of 0 and 30% had a PD-L1 of more than 50%. Additionally, 4 patients had epidermal growth factor receptor mutations, including 2 classical exon 19 deletions and 2 patients with EML4-ALK (anaplastic lymphoma kinase) translocations.

All 20 patients enrolled received nivolumab and 16 of those patients went on to recive TIL. Of the 4 patients who did not go on to receive TIL, 1, was still responding to nivolumab, 1 had insufficient TIL growth, 1 had a decline in performance status, and 1 had a loss of insurance/transportation.

Sixteen patients were evaluated for clinical activity. Of the 16 patients, 11 had initial tumor regression at the first CT scan, which was performed 1 month after TIL ACT. The median best change in sum of target lesion diameters was -35.5% (range, +20 to -100). Radiographic response was seen in 6 of the 13 patients evaluated for radiographic response. Of those 13 patients, 2 had ongoing complete response ate 1.5 years, 2 had an unconfirmed partial response due to subsequent new brain metastases, and 2 more patients maintained a clinical remission by local ablative therapy of a new escapes lesion. This therapy was performed between 6 and 17 months after TIL infusion.

Of the 16 patients evaluated for safety, 100% experienced a grade 4 decrease in lymphocyte count and 94% experienced a grade 4 decrease in white blood cell depletion. Eighty-one percent of patients experienced grade 3 anemia. Other common grade 3/4 adverse events included platelet count decrease (69%), neutrophil count decrease (69%), and hypophosphatemia (50%).

“We found that excisional tumor biopsy and nivolumab followed by administration of cyclophosphamide, fludarabine, IL-2 with TIL infusion in pretreated metastatic lung cancer was feasible in an academic center setting and had manageable adverse effects. We observed that lymphocytes could be successfully expanded from most patients’ tumors and were largely capable of autologous tumor recognition,” wrote study authors. “In addition to two durable complete responses, we also observed some patients who derived clinical benefit in a variety of other ways, including local ablation of a single metachronous new lesion.”

REFERENCES:
1.Creelan B.C., Wang C, Teer J.K., et al. Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial. Nat Med 2021;27:1410–1418 https://doi.org/10.1038/s41591-021-01462-y
2.Nivolumab and Tumor infiltrating lymphocytes (TIL) in advanced non-small cell lung cancer. ClinicalTrials.Gov. Accessed August 27, 2021. https://bit.ly/3yoV0t5.

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