Tidutamab Shows Promise Treating Advanced Neuroendocrine Tumors

Tidutamab (Xencor, Inc) showed a promising safety and tolerability profile in patients with advanced, well-differentiated neuroendocrine tumors (NETs) of pancreatic, gastrointestinal, lung, and undetermined origin in a phase 1 study. The data on tidutamab, a tumor-targeted bispecific antibody, are being presented during the North American Neuroendocrine Tumor Society’s 2021 Multidisciplinary NET Medical Virtual Symposium (NANETS).

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

“The phase 1 study of tidutamab in patients with neuroendocrine tumors informed our view that an XmAb CD3 bispecific antibody is generally well-tolerated in solid tumors, with a low incidence and severity of CRS, and can induce meaningful biological activity in a challenging disease setting,” said Allen Yang, MD, PhD, senior vice president and chief medical officer at Xencor, in a press release. “Importantly, we identified a recommended dose for continued study, and a phase 1b/2 study has been opened to evaluate tidutamab as a potential treatment option for patients with Merkel cell carcinoma and small cell lung cancer, SSTR2-expressing tumor types known to be responsive to immunotherapy."

The phase 1 study seeks to evaluate the safety and tolerability profile of the drug and to identify the maximum tolerated dose and/or recommended dosing regimen for continued study among patients with advanced, well-differentiated NETs. The researchers determined the ideal dosing regimen to be a 0.3 mcg/kg priming dose followed by 1.0 mcg/kg on subsequent dosing days.

As of August 2021, 41 patients with NETs with an initial lesion located in the pancreas (46%), intestine (22%), lung (20%), and other GEP-NET or unknown (12%) were administered doses of tidutamab ranging from 0.1 mcg/kg to 2.0 mcg/kg.

Dosing consisted of a lower priming dose followed by a higher repeated dose on subsequent days. Twenty patients in the expansion cohort were administered the recommended dosing regimen. This group had a median age of 64 years and a median of 4 prior lines of systemic therapies. Further, 50% of patients were previously administered peptide receptor radionuclide therapy.

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

Cardiorenal syndrome (CRS) of any grade was observed in 41% of patients, with most cases limited to grade 1 and grade 2 and primarily observed as occurring following the first 2 doses. Grade 3 CRS was observed in 2 patients (5%) with the first dose; however, all patients who experienced CRS fully recovered. An analysis of peripheral blood biomarkers showed that tidutamab induced acute and sustained T-cell activation at the recommended dose for expansion, according to the study.

Tidutamab is also being evaluated in an ongoing phase 1b/2 study that is currently enrolling patients with Merkel cell carcinoma and small cell lung cancer, which have SSTR2-expressing tumor types previously found to be responsive to immunotherapy, according to Xencor.

A poster presentation with these data will be presented during the NANETS Clinical Abstracts session, at 1:25 pm ET on November 6, 2021.

Reference

Xencor Presents Clinical Data from the Phase 1 Study of Tidutamab in Neuroendocrine Tumors at NANETS’ Multidisciplinary NET Medical Virtual Symposium. Yahoo Finance. News release. November 3, 2021. Accessed November 4, 2021. https://finance.yahoo.com/news/xencor-presents-clinical-data-phase-130000761.html