Xencor picks 400 mcg/kg as Phase 3 dose for kidney cancer drug XmAb819

What Xencor reported at ESMO

Xencor announced the results in a press release dated 25 October. Sumanta Pal of City of Hope presented them that Sunday in a proffered paper session at the European Society for Medical Oncology Congress 2026 in Madrid, and the company discussed them on an investor webcast the next morning.

XmAb819 is a bispecific antibody that binds ENPP3 on tumour cells with two arms and CD3 on T cells with one, steering immune cells at the cancer. ENPP3 is strongly expressed in ccRCC and at low levels on normal tissue, according to the company.

As of a 1 September data cut, the Phase 1 study had enrolled 119 patients with advanced ccRCC across 11 intravenous target dose levels. Three doses went into expansion, 100, 200 and 400 mcg/kg, covering 68 patients. Those patients had a median of three prior lines of therapy, and 94% were intermediate- or poor-risk on the IMDC scale. At 400 mcg/kg the confirmed objective response rate was 45.5%, based on five confirmed partial responses among 11 evaluable patients plus one unconfirmed partial response, which lifts the rate to 55% if unconfirmed results count. The 95% confidence interval on the 45.5% figure ran from 16.8% to 76.6%. The six-month progression-free survival estimate at that dose was 82%, and median PFS had not been reached. Lower doses produced 30% confirmed response at 100 mcg/kg among 30 evaluable patients and 44% at 200 mcg/kg among 25.

Why the dose choice matters

Xencor said it picked 400 mcg/kg because response rate increased with increasing dose and all expansion doses were generally well tolerated. Pal said the 400 mcg/kg group showed tumour shrinkage in nearly all patients and included ongoing responses. Xencor plans to discuss accelerated approval with the FDA in the first half of 2027 and to start a registration-enabling study, including a global randomized trial against tivozanib, by the end of 2027.

Xencor says no treatment is recommended in guidelines for patients whose disease progressed after a PD-(L)1 inhibitor and at least two VEGFR TKIs.

In that group XmAb819 had a 45% confirmed response rate across 42 patients, the company said. That subgroup is the one Xencor wants to discuss with the FDA for an accelerated pathway. Tivozanib, the comparator Xencor will test against, posted 10.5% response and 41% six-month PFS on similar measures in the TiNivo-2 trial. The two trials enrolled different populations, so the comparison is a rough guide. Bassil Dahiyat, Xencor's chief executive, said the company expects XmAb819 to become the third XmAb 2+1 candidate to move into late-stage development.

Safety and the limits of the data

Across the 68 patients in the three expansion cohorts, 72.1% had Grade 3 or worse treatment-related adverse events. Only 5.9% stopped treatment because of those events. The most common severe events were liver-enzyme elevations, rash, low blood pressure and cytokine release syndrome, and they occurred mainly during the priming period. One patient received roughly ten times the intended exposure after a suspected preparation error, developed Grade 4 cytokine release syndrome, recovered and discontinued treatment. Xencor said about 25% of responses came after more than four months on treatment and that responses deepened over time in some patients.

The 45.5% response rate still comes from 11 patients, with no control arm. At the selected dose, more than 70% of patients remained on treatment, with more than six months of median follow-up, Xencor said.

The market reaction and the balance sheet

Xencor shares rose $4.94, or 19.62%, to $30.12 in morning trading on 26 October, after touching a 52-week high of $32.29, IBTimes reported. More than 4.1 million shares changed hands, about three times the stock's three-month daily average, and market value rose to about $2.25 billion. The stock was up about 76% over the previous 52 weeks. The move came after Xencor closed at $25.18 on 23 October, before the data. Wedbush had reiterated an outperform rating and a $30 target before the investor webcast; Truist raised its target to $29 from $27 in late September. Xencor says its cash runway extends into 2029.

What happens next

Xencor expects at least 20 efficacy-evaluable patients at 400 mcg/kg in the first half of 2027, alongside its FDA talks. Subcutaneous formulation data are also due in that half. Xencor also plans studies combining XmAb819 with PD-1 immunotherapy and in other ENPP3-positive tumours, including colorectal, lung and papillary kidney cancer. The ENPP3-positive sub-study opened in the second quarter of 2026 and the IO-doublet sub-study in the third quarter.