Xencor, a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases, today announced that initial data from its ongoing Phase 1 dose-escalation study of tidutamab (XmAb^®18087), an SSTR2 x CD3 bispecific antibody, in patients with neuroendocrine tumors (NETs) will be presented during the upcoming North American Neuroendocrine Tumor Society’s 2021 Multidisciplinary NET Medical Virtual Symposium (note – it was also presented at NANETS 2020). 

What are monocloncal antibodies?  See here

About Tidutamab

Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance or mimic the immune system’s attack on cancer cells. They are designed to bind to antigens that are generally more numerous on the surface of cancer cells than healthy cells, i.e. they are a targeted treatment.  Tidutamab (XmAb^®18087) is a tumor-targeted bispecific antibody that contains both an SSTR2 binding domain and a T-cell binding domain (CD3). An XmAb^® bispecific Fc domain serves as the scaffold for the two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on tidutamab. SSTR2 (somatostatin receptor 2) is an antigen highly expressed on some solid tumors, and engagement of CD3 by tidutamab activates T cells for highly potent and targeted killing of SSTR2-expressing tumor cells. Tidutamab is being evaluated in an ongoing Phase 1 study, which is enrolling patients with neuroendocrine tumors (NETs) and gastrointestinal stromal tumors (GISTs). As this is an SSTR targeted therapy, it follows that it is designed to work with well differentiated NETs which have not yet been well served by the introduction of immunotherapy. 

About the Clinical Trial

The clinical trial is listed in Clinical Trials dot Gov under number NCT03411915 with a title of “A Study of XmAb®18087 in Subjects With NET and GIST“.  It is recruiting and they are looking for 87 participants. This is a Phase 1, multiple dose, ascending dose escalation study; to define a dose tolerance and a regimen consisting of a first “priming” dose and escalated subsequent doses of XmAb18087; to describe safety and tolerability; to assess PK (pharmacokinetic) and immunogenicity; and to preliminarily assess anti-tumor activity of XmAb18087 in subjects with advanced NET or GIST. Which NET types qualify?  Histologically or cytologically confirmed well differentiated low or intermediate grade (World Health Organization [WHO] Grade 1 or 2) NET of pancreatic, gastrointestinal, lung, or undetermined origin (unknown primary) that is locally advanced or metastatic and has progressed within the past 12 months.  And histologically confirmed GIST that is locally advanced or metastatic.  Other inclusion requirements exist and can be found in the clinical trials document.  Where is the trial conducted?   There are currently 16 sites across the US, they all look like well-known hospitals for treating NETs.  The full list is in the clinical trials document. 

A follow on 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 trial will include pembrolizumab (Keytruda). 

About Xencor, Inc.

Xencor is a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases. Xencor’s XmAb antibody engineering technology enables small changes to the structure of monoclonal antibodies resulting in new mechanisms of therapeutic action. For more information, please visit www.xencor.com.

Xencor to Present Initial Data from the Phase 1 Study of Tidutamab in Neuroendocrine Tumors at NANETS’ Multidisciplinary NET Medical Virtual Symposium

Presentation Details – A poster (copy below) with data from the study is available in the NANETS Virtual Poster Hall, and it will be made available under Archived Scientific Presentations on the Events & Presentations page in the Investors section of www.xencor.com. In addition to the poster, these results will be presented during the Clinical Abstracts session, which begins at 1:25 p.m. ET on Saturday, November 6, 2021.

Quote from the clinical trial:  “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, M.D., Ph.D., senior vice president and chief medical officer at Xencor. “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 primary objectives of the Phase 1 study were to determine the safety and tolerability profile of tidutamab in patients with advanced, well-differentiated NETs of pancreatic, gastrointestinal, lung and undetermined origin, and to identify the maximum tolerated dose and/or recommended dosing regimen for continued study, which was determined to be a 0.3 mcg/kg priming dose followed by 1.0 mcg/kg on subsequent dosing days.

At data cut-off in August 2021, 41 patients with neuroendocrine tumors, with the initial lesion location in the pancreas (46%), intestine (22%), lung (20%), and other GEP-NET or unknown (12%), received doses of tidutamab ranging from 0.1 to 2.0 mcg/kg. Dosing in the study included a lower priming dose, followed by a higher repeated dose on subsequent dosing days. The 20 patients in the expansion cohort received the recommended dosing regimen. Patients had a median age of 64 years and a median of four prior lines of systemic therapies. Fifty percent of patients received prior peptide receptor radionuclide therapy.