Xencor reports 45.5% confirmed response at selected kidney-cancer dose
Severe or worse treatment-related adverse events affected 72.1 per cent across expansion cohorts; FDA talks are planned for 2027.
Adrian Kessler
Confirmed tumour shrinkage in five of 11 evaluable kidney-cancer patients supported dose selection as Xencor, Inc. NASDAQXNCR reported Phase 1 results on Sunday. Severe or worse treatment-related adverse events occurred in 72.1 per cent of patients across the combined dose-expansion cohorts.
The Oct. 25 release selected 400 micrograms per kilogram intravenously as the proposed Phase 3 dose for XmAb819. Xencor plans discussions with the FDA about a potential accelerated approval pathway in selected patient subgroups in the first half of 2027.
Xencor is a small, Pasadena-based clinical-stage biotechnology company developing engineered antibodies for cancer and autoimmune diseases. Its experimental antibody is designed to connect ENPP3-expressing tumour cells with CD3-bearing immune T cells.
Ahead of the announcement, Xencor shares closed at US$25.18 on Nasdaq at 4:00 p.m. EDT on Oct. 23, according to NASDAQXNCR. That price predates the results; management says its cash runway extends into 2029.
Responses Come From Small, Uncontrolled Cohorts
The study had enrolled 119 patients across 11 target-dose levels by Sept. 1. The expansion groups had received a median of three prior treatment lines, and every patient had previously received both a checkpoint inhibitor and a VEGF-receptor tyrosine kinase inhibitor.
At the selected dose, the confirmed response rate was 45.5 per cent, with a 95 per cent confidence interval from 16.8 to 76.6 per cent. Investigators assessed responses using RECIST tumour-measurement criteria.
The lower-dose cohorts tested 100 and 200 micrograms per kilogram. Their confirmed response rates were 30 and 44 per cent, respectively, among 30 and 25 evaluable patients.
There was no control arm. The registry record, updated Aug. 3, identifies safety and dose-limiting toxicities as primary outcomes, with response and progression-free survival among secondary outcomes.
An Oct. 1 update still showed five confirmed partial responses in the selected-dose cohort, plus one unconfirmed partial response. The six-month progression-free survival estimate was 82 per cent, but median progression-free survival had not been reached. Median follow-up at the selected dose was six months at the Sept. 1 cutoff.
Read more: Lilly reports 14.5-month response duration with olomorasib lung-cancer combination
The small cohort and wide response interval leave substantial uncertainty about the effect in a larger population. Without randomization, these results cannot establish superiority over existing treatments.
Read more: Genmab reports 75 per cent first-line response in petosemtamab colorectal study
Treatment-related adverse events caused discontinuation in 5.9 per cent of the combined expansion cohorts. Severe events included liver-enzyme elevations, rash, low blood pressure and cytokine release syndrome, an inflammatory reaction associated with immune activation.
The release also described an excluded patient who received approximately ten times the intended exposure after a suspected preparation error. That patient developed Grade 4 cytokine release syndrome, recovered and discontinued treatment.
Randomized Development Would Test The Competitive Position
Merck & Co., Inc. NYSEMRK provides a later-line kidney-cancer benchmark through Welireg. Its Dec. 14, 2023 approval announcement reported response rates of 22 per cent with Welireg versus 4 per cent with everolimus in a randomized trial.
Exelixis, Inc. NASDAQEXEL markets another established option, Cabometyx, a tyrosine kinase inhibitor used in advanced kidney cancer. Differences in patient selection and study design prevent a direct efficacy ranking against Xencor's early results.
Xencor plans a global randomized study comparing XmAb819 alone with tivozanib after prior checkpoint-inhibitor and VEGF-receptor-inhibitor treatment. The company describes the accelerated approval pathway as a topic for its planned FDA discussions in 2027.
“We plan to initiate a potential registration-enabling study next year,” Xencor president and chief executive officer Bassil Dahiyat said in the release.
The next scheduled event is Xencor's Oct. 26 webcast at 7:00 a.m. EDT. Management plans to discuss additional data and development plans, giving holders the next opportunity to assess the evidence behind the proposed dose.
