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.

Videos

Kedar Kirtane, MD, discusses the design of a phase 1b trial evaluating the TIL Tbio-4101 plus pembrolizumab in patients with advanced HNSCC.

Dr Kirtane on an Investigation of TILs Plus Pembrolizumab in Advanced HNSCC

Kedar Kirtane, MD, assistant member, Department of Head and Neck-Endocrine Oncology, medical director, Solid Tumor Cellular Therapy, Moffitt Cancer Center, discusses a phase 1b study investigating TBio-4101, which isolates autologous selected and expanded tumor-infiltrating lymphocytes (TILs), plus pembrolizumab (Keytruda) in patients with PD-1 inhibitor–resistant, advanced head and neck squamous cell carcinoma (HNSCC). This trial’s rationale and design were shared at the 

Currently, patients with recurrent metastatic head and neck cancers have limited treatment options, with the standard of care being pembrolizumab (Keytruda), with or without chemotherapy, Kirtane begins. Unfortunately, most of these patients experience disease progression despite receiving this treatment, he says, adding that as of now, there is no effective second-line therapy available to manage their condition. Ongoing research efforts aim to address this unmet need, particularly for patients who do not respond to PD-1 inhibition and subsequent treatments, Kirtane reports.

The primary objective of this phase 1b trial is to develop a readily available second-line treatment for patients with advanced HNSCC whose cancers progress after standard therapies, he expands. TIL therapy offers a promising approach, Kirtane states. This therapy involves extracting lymphocytes from a patient’s tumor, enhancing the cancer-fighting capabilities of these lymphocytes, and reintroducing them into the patient’s body, he elucidates.

TBio-4101 stands out because it uses a selection process to isolate lymphocytes that are more likely to reduce tumors effectively, Kirtane explains. This selective process contrasts with those of other TIL products that do not differentiate between more and less effective lymphocytes, according to Kirtane. By focusing on the most potent lymphocytes, TBio-4101 aims to provide a more effective treatment option for patients with recurrent metastatic HNSCC, he states.

The rationale behind this trial is to fill the critical gap in treatment options for these patients, offering a new line of defense against their disease, Kirtane says. By leveraging the unique properties of TIL therapy combined with advanced selection techniques, investigators hope to significantly improve outcomes for patients who have exhausted other treatment avenues, Kirtane concludes.

Kedar Kirtane, MD, discusses a phase 1b study of TBio-4101 plus pembrolizumab in patients with PD-1 inhibitor–resistant, advanced HNSCC.

Kedar Kirtane, MD, assistant member, the Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, discusses the design of the phase 1/2 EVEREST-1 trial (NCT05736731), which is evaluating the autologous CAR T-cell therapy A2B530 in patients with advanced solid tumors.

EVEREST-1 features a unique design for a CAR T-cell therapy clinical trial, Kirtane begins. A master screening protocol serves as the first step for potential enrollment in the study, referred to as the BASECAMP-1 trial (NCT04981119). In the observational BASECAMP-1 study, patients with advanced solid tumors with a high risk of relapse are undergoing extensive screening to identify those with tumors expressing human leukocyte antigen (HLA) loss of heterozygosity.

During BASECAMP-1, enrolled patients are undergoing apheresis to store T cells for future use to produce A2B530 as part of EVEREST-1. Notably, there is no time limit between enrollment in BASECAMP-1 and EVEREST-1, and eligible patients will be allowed to enroll in EVEREST-1 upon disease progression. EVEREST-1 is including patients with colorectal cancer, pancreatic cancer, non–small cell lung cancer, and other solid tumors with CEA expression and a loss of HLA-A*02 expression.

A2B530 features a unique mechanism designed to distinguish tumor cells from healthy cells, Kirtane expands. The CAR T-cell therapy is meant to target tumors that express CEA and do not have HLA-A*02 expression. That mechanism inspired the observational BASECAMP-1 trial as a prescreening protocol to better identify patients who would be eligible to receive A2B530, allowing patients to enroll in EVEREST-1 following disease progression, Kirtane says.

Loss of heterozygosity is a common occurrence in patients with cancer, Kirtane continues, noting that it occurs in approximately 20% of patients with solid tumors. By identifying patients with this unique mutation, it allows EVEREST-1 to enroll patients more likely to benefit from this treatment, Kirtane concludes.

Kedar Kirtane, MD, discusses the design of the phase 1/2 EVEREST-1 trial, which is evaluating the autologous CAR T-cell therapy A2B530 in patients with advanced solid tumors.

Kedar Kirtane, MD

Articles

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

Dr Kirtane on an Investigation of TILs Plus Pembrolizumab in Advanced HNSCC

Dr Kirtane on the Design of the EVEREST-1 Trial Evaluating A2B530 in Solid Tumors