Xencor picks 400 mcg/kg XmAb819 dose on a 45.5% response rate from 11 patients

Xencor said it will advance XmAb819 at 400 mcg/kg into late-stage development after the intravenous dose produced a 45.5% confirmed objective response rate in 11 evaluable patients with advanced clear cell renal cell carcinoma. The Phase 1 update was presented at the ESMO Congress 2026 in Madrid and published in an October 25, 2026 release that Xencor filed as Exhibit 99.2 to the 8-K, alongside an October 26 investor presentation it furnished as Exhibit 99.1.

The dose Xencor will carry into late-stage testing is 400 mcg/kg, not either of the two lower expansion levels it also tested. The supporting Phase 1 data were presented at the ESMO Congress 2026 in Madrid, and the full update sits in an October 25 release filed with the 8-K and an October 26 slide deck that the company furnished to the SEC.

Eleven patients carry the 45.5% response rate

As of a September 1, 2026 data cut, the study had enrolled 119 patients across 11 intravenous dose levels. Three doses went into expansion - 100 mcg/kg (n=30), 200 mcg/kg (n=25) and 400 mcg/kg (n=11) - 66 efficacy-evaluable patients drawn from the 68-patient Expansion Dose analysis set, after two 200 mcg/kg patients were excluded for missing a post-baseline tumor assessment; every one of them had received at least one prior PD-(L)1 inhibitor and at least one prior VEGFR TKI, with a median of three prior lines. Confirmed response climbed with dose: 30% at 100 mcg/kg, 44% at 200 mcg/kg and 45.5% at 400 mcg/kg, where the 95% confidence interval ran from 16.8% to 76.6%. An October 1, 2026 cut added one unconfirmed partial response at 400 mcg/kg for a 55% unconfirmed rate, with median progression-free survival not reached and a 6-month Kaplan-Meier PFS estimate of 82%, an estimate resting on a cohort with 6.0 months of median follow-up. Across the expansion doses, 25 patients responded - one complete and 24 partial - and 19 responses were still ongoing. "XmAb819 has demonstrated impressive antitumor activity in a heavily pre-treated and difficult-to-treat patient population with advanced clear cell renal cell carcinoma," study investigator Sumanta Pal of City of Hope said.

Liver enzymes and three dose-preparation errors

Xencor described XmAb819 as generally well tolerated, with manageable adverse events. Related Grade 3 or higher treatment-emergent events still reached 72.1% of expansion patients, led by AST increases at 35.3% and ALT increases at 33.8%, with rash at 22.1% and cytokine release syndrome at 5.9%; 5.9% stopped treatment because of a related event. Xencor said the transaminase rises were asymptomatic and self-limited, resolving in a median of seven days. The release also disclosed suspected dose-preparation errors in three of the 69 patients in the Expansion Dose cohorts; one received roughly 10-fold the intended exposure, developed Grade 4 cytokine release syndrome, recovered and discontinued. All three occurred before a new formulation was introduced.

Tivozanib is the comparator, and 2027 is the gate

Xencor plans to discuss an accelerated approval pathway with the FDA in the first half of 2027 and to start a global randomized trial against tivozanib in patients who have had one PD-(L)1 inhibitor and at least one VEGFR TKI; subject to those talks, the trial could support full approval. The company points to a TiNivo-2 sub-group analysis in a similar line where tivozanib produced a median PFS of 5.4 months, a 6-month PFS estimate of 41% and a cORR of 10.5%, against 82% at six months and 45.5% for XmAb819 - 2.0x on the PFS estimate. Xencor cautions that cross-trial comparison is provided for illustration only. Pooled expansion patients with at least two prior VEGFR TKIs (n=42) had a 45% cORR, and triple-class exposed patients (n=23) 35%. At least 20 patients at 400 mcg/kg should be evaluable in the first half of 2027, with a registration-enabling study targeted by the end of 2027.

No quarterly figures inside the 8-K

The Form 8-K filed October 26, 2026 carries Item 2.02, Item 7.01 and Item 8.01, and Item 9.01 listing the presentation and the press release. Despite the results-of-operations label, the Item 2.02 disclosure contains a single forward-looking sentence: cash is expected to fund research and development programs and operations into 2029. There is no revenue, net loss, earnings-per-share or cash-balance table in the filing, and no quarterly financial statements were furnished. The presentation makes the commercial case instead, estimating about 9,200 U.S. patients were treated after a PD-(L)1 inhibitor and at least two VEGFR TKIs in 2025 and putting the global RCC drug market at roughly $11.7B annualized; both are company estimates. Chief executive Bassil Dahiyat framed the spending plan this way: "With cash runway into 2029, we are well positioned to continue to pursue an accelerated pace of clinical development across our portfolios in oncology and autoimmune disease."