Tidutamab shows promise in treating advanced neuroendocrine tumors

Tidutamab has been shown to have favorable safety and tolerability in the treatment of neuroendocrine tumors of pancreatic, gastrointestinal, pulmonary and indeterminate origin.

Tidutamab (Xencor, Inc) has shown a promising safety and tolerability profile in patients with advanced and well-differentiated neuroendocrine tumors (NETs) of pancreatic, gastrointestinal, pulmonary and indeterminate origin in a phase 1 study Data on tidutamab, a bispecific tumor targeting antibody, is presented at the North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary Virtual Medical Symposium NET 2021.

Tidutamab contains a somatostatin 2 receptor binding domain (SSTR2) and a T cell binding domain (CD3). An XmAb bispecific Fc domain serves as a link between the antigen-binding domains and contributes to the prolonged circulating half-life, stability and ease of manufacture of the drug, according to Xencor. By engaging with CD3, tidutamab activates T cells to target tumor cells expressing SSTR2, according to Xencor.

“The Phase 1 study of tidutamab in patients with neuroendocrine tumors informed our opinion that an XmAb CD3 bispecific antibody is generally well tolerated in solid tumors, with a low incidence and severity of CRS, and may induce activity significant biological in a difficult pathological context. “Allen Yang, MD, PhD, senior vice president and medical director of Xencor, said in a press release.” It is important to note that we have identified a recommended dose for the study to continue, and one phase 1b / 2 study was initiated to evaluate tidutamab as a potential treatment option for patients with Merkel cell carcinoma and small cell lung cancer, tumor types expressing SSTR2 known to be susceptible to immunotherapy. “

The phase 1 study aims to assess the safety and tolerability profile of the drug and to identify the maximum tolerated dose and / or the recommended dosage regimen for the continuation of the study in patients with advanced and well differentiated NETs. . The researchers determined that the ideal dosing regimen was a starting dose of 0.3 mcg / kg followed by 1.0 mcg / kg on subsequent dosing days.

In August 2021, 41 NET patients with an initial lesion localized in the pancreas (46%), intestine (22%), lungs (20%) and other NET-GEP or unknown (12%) had received doses of tidutamab ranging from 0.1 mcg / kg to 2.0 mcg / kg.

The dosage consisted of a lower initiation dose followed by a repeated higher dose on the following days. Twenty patients in the extension cohort received the recommended dosage regimen. This group had a median age of 64 years and a median of 4 prior lines of systemic therapy. In addition, 50% of patients have already received peptide receptor radionuclide therapy.

Tidutamab at a dose of 0.3 / 1.0 mcg / kg has been shown to be generally well tolerated. The most common Grade 3 or Grade 4 treatment-related adverse events (AEs) across all dose ranges were lymphopenia (29%), increases in gamma-glutamyl transferase (20%), increases in transaminases (20%) and vomiting (17%). In addition, grade 3 esophageal dysmotility was found in 7% of patients.

Cardio-renal syndrome (CRS) of any grade was observed in 41% of patients, most cases being limited to grades 1 and 2 and mainly seen after the first 2 doses. Grade 3 CRS was observed in 2 patients (5%) with the first dose; however, all of the patients who presented with CRS made a full recovery. Peripheral blood biomarker analysis showed that tidutamab induced acute and sustained activation of T cells at the dose recommended for expansion, according to the study.

Tidutamab is also being evaluated in an ongoing Phase 1b / 2 study that is currently recruiting patients with Merkel cell carcinoma and small cell lung cancer, who have SSTR2-expressing tumor types that have previously responded to immunotherapy, according to Xencor.

A poster presentation with this data will be presented during the NANET Clinical Summaries session at 1:25 p.m. ET on November 6, 2021.

Reference

Xencor presents clinical data from the Phase 1 study of Tidutamab in neuroendocrine tumors at the NANETS NET Multidisciplinary Virtual Medical Symposium. Yahoo finances. Press release. November 3, 2021. Accessed November 4, 2021. https://finance.yahoo.com/news/xencor-presents-clinical-data-phase-130000761.html


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