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Xencor (XNCR) is surging after announcing updated results from its Phase 1 study of XmAb819, an ENPP3 x CD3 T-cell engaging bispecific antibody, in patients with advanced clear cell renal cell carcinoma (ccRCC). The company also selected 400 mcg/kg as its proposed intravenous Phase 3 dose and outlined plans for a potentially registration-enabling study by the end of 2027.

• XmAb819 is an experimental bispecific antibody designed to activate the body's immune system against cancer cells. It targets ENPP3, a protein highly expressed on kidney cancer cells, and CD3 on T cells, with the goal of recruiting immune cells to recognize and destroy tumors.
• The Phase 1 study enrolled 119 patients across 11 intravenous dose levels, with 68 patients included in three expansion cohorts receiving 100, 200, or 400 mcg/kg. Patients had received a median of three prior lines of treatment. Confirmed objective response rates were 30%, 44%, and 45.5%, respectively, with the higher doses demonstrating stronger antitumor activity than the lowest dose.
• At the 400 mcg/kg dose, the disease control rate reached 82%, with an estimated six-month progression-free survival rate of 82%. These findings, based on 11 evaluable patients, supported the company's selection of the dose for further development. Regarding safety, 72.1% of patients across the expansion cohorts experienced Grade 3 or higher treatment-related adverse events, although only 5.9% discontinued treatment due to related adverse events.
• Looking ahead, Xencor plans to discuss a potential accelerated approval pathway with the FDA in 1H27 for heavily pretreated patients and initiate a global randomized trial comparing XmAb819 with tivozanib by the end of 2027. The company is also evaluating the treatment in additional cancers, including colorectal and non-small cell lung cancer, as well as earlier treatment settings.

Briefing.com Analyst Insight

Overall, XmAb819 showed its highest response rate at the 400 mcg/kg dose, supporting Xencor's decision to advance the treatment toward Phase 3 development. The planned randomized trial could eventually support approval in the second- and third-line setting, presenting a meaningful longer-term opportunity for the company. That opportunity could expand further as Xencor explores the treatment in earlier settings and additional cancer types. However, the results at the selected dose remain preliminary, with only 11 evaluable patients, while the high incidence of severe treatment-related adverse events remains an important consideration. Much of the upside will likely depend on whether XmAb819 can demonstrate similar efficacy and an acceptable safety profile in larger, controlled studies.