Dr Kirtane on the Design of a Phase 1b Trial of Tbio4101 Plus Pembrolizumab in HNSCC

Kedar Kirtane, MD, assistant member, Department of Head and Neck-Endocrine Oncology; medical director, Solid Tumor Cellular Therapy, Moffitt Cancer Center, discusses the design of a phase 1b trial (NCT06236425) evaluating the tumor-infiltrating lymphocyte (TIL) Tbio-4101 plus pembrolizumab (Keytruda) in patients with PD-1 inhibitor–resistant, advanced head and neck squamous cell carcinoma (HNSCC), as well as unmet needs that this research aims to address.

This phase 1b trial is enrolling patients who are about to begin treatment for recurrent/metastatic HNSCC, Kirtane says. Investigators will biopsy patient tumors and perform apheresis to isolate the lymphocytes that are most likely to be effective and filter out non–tumor-reactive bystander T cells, Kirtane explains. This process is performed to manufacture Tbio-4101, a personalized T-cell product that is enriched for polyclonal, polyfunctional, tumor-reactive T cells. Tbio-4101 uses a range of endogenous neoantigen-reactive T cells that can target several tumor antigens, and may be able to affect change in immunologically “cold” tumors. The Tbio-4101 manufacturing process uses single-cell sorting of individualized neoepitope-reactive TILs. After apheresis, patients will receive standard-of-care (SOC) pembrolizumab with or without chemotherapy.

Patients who exhibit favorable responses with this SOC regimen will continue to receive it, Kirtane notes. However, most patients do not experience optimal outcomes with this first-line treatment approach, Kirtane emphasizes. In this trial, the patients who progress on frontline therapy will then have the option to receive Tbio-4101 as second-line treatment, shortening their wait time between lines of therapy, according to Kirtane.

Patients with advanced HNSCC have several unmet needs and are especially in need of more effective second-line therapies, Kirtane says. TIL products are a viable treatment option for these patients, as they leverage patients’ immune systems, Kirtane adds. Since TIL products are enriched for tumor-reactive T cells, they may be effective against patients’ tumors, Kirtane concludes.