Bye-bye: Xencor culls 2 bispecifics after early-phase solid tumor data underwhelm

Two bispecific antibodies have failed to make the grade at Xencor. The biotech is culling the pair of drug candidates in response to early-phase solid tumor studies that suggested they lack a competitive clinical profile.

Xencor moved the bispecific antibody tidutamab into a phase 1 clinical trial for neuroendocrine and gastrointestinal stromal tumors in 2018, before going on to initiate a Keytruda combination study in advanced Merkel cell carcinoma and extensive-stage small cell lung cancer patients two years later. The idea was to activate T cells via the protein complex CD3 and turn them against cells expressing SSTR2, an antigen that is highly expressed on some solid tumors. 

Early results in neuroendocrine tumors arrived in 2020 and, despite the best response being stable disease, Xencor pushed on to a second data drop that arrived late last year. The second drop only added to the doubts, with no partial or complete responses, the best response still being stable disease, and the disease control rate falling from 43% to 27% between the two readouts. As a result, Xencor halted the program.

Other biotechs have also struggled to trigger partial responses by targeting SSTR2. Tarveda Therapeutics took a SSTR2-directed small-molecule drug conjugate into a clinical trial in 2016 but saw no responses and three cases of stable disease among 12 small cell lung cancer patients in the dose-expansion cohort.

Xencor is also stopping work on another bispecific antibody, XmAb841, in light of clinical data. The candidate was in development as a monotherapy and in combination with Keytruda in a range of solid tumors, reflecting Xencor’s belief that it may promote tumor-selective T-cell activation by simultaneously targeting the immune checkpoint receptors CTLA-4 and LAG-3. 

Faced with disappointing data on the two bispecifics, Xencor has decided to stop internal development and focus its resources on new clinical programs. The biotech will continue to support patients currently enrolled and being treated.