XBiotech Phase 1/2 Study Shows Potential Breakthrough for Advanced Pancreatic Cancer

On June 18, 2024, XBiotech (NASDAQ: XBIT) released data from its Phase 1/Phase 2 clinical trial of Natrunix for advanced pancreatic cancer. This study, called 1-BETTER, evaluated the efficacy of Natrunix (an anti-interleukin-1alpha antibody) combined with a standard chemotherapy regimen (ONIVYDE + 5-Fluorouracil + Leucovorin). The chemotherapy regimen, although effective, is often associated with challenging side effects and suboptimal survival rates. Natrunix aimed to not only act as an anti-cancer agent but also improve the tolerability of the chemotherapy.

The Phase 1 portion focused on dose escalation to identify any dose-limiting toxicities (DLTs) in patients with metastatic pancreatic cancer. No DLTs were observed, allowing the highest dose used in Phase 1 to be carried forward into Phase 2.

In the Phase 2 part, 65 subjects were randomized into two groups: one receiving Natrunix with the chemotherapy regimen (Arm1) and the other receiving a placebo with the same regimen (Arm2). The treatment spanned 24 weeks, with patients receiving therapy every other week.

Participants had confirmed metastatic, unresectable, or recurrent pancreatic adenocarcinoma and had progressed after prior gemcitabine-based treatments. They were required to have at least one measurable tumor according to RECIST v1.1 criteria.

The primary goal of Phase 2 was to assess the safety and tolerability of the Natrunix combination. Results showed fewer adverse events in the Natrunix group (297 vs. 336). Significant adverse events were reduced by 28%, with 9 out of 33 subjects in the Natrunix group experiencing such events compared to 12 out of 32 in the placebo group. Hospitalization days were also reduced by 33% (80 days vs. 120 days).

Additionally, the Natrunix group reported a 22% reduction in fatigue, a 32% improvement in appetite, and a 41% reduction in pain by the end of the treatment period. Severe diarrhea, a common complication with the chemotherapy regimen, was halved (9% vs. 19%) in the Natrunix group.

Overall Survival (OS), a secondary endpoint, was measured from randomization to death. A Kaplan-Meier Survival Curve highlighted that none of the placebo group survived beyond 330 days, whereas 8 subjects in the Natrunix group were still alive at that point. The p-value of 0.096 indicated a trend towards improved survival in the Natrunix group despite the small sample size.

Lead investigator Dr. David J. Park emphasized the significance of these findings, noting the challenges of treating advanced pancreatic cancer and the promising reduction in toxicity and potential survival benefits seen with Natrunix.

Although the Phase 2 study had a limited number of participants, the results suggested better outcomes for the Natrunix group in terms of fewer serious adverse events, reduced hospitalization, and improved overall survival. XBiotech views these findings as indicative of Natrunix's potential to advance pancreatic cancer treatment.

XBiotech is dedicated to developing targeted antibodies through its True Human™ technology, aiming to create natural human antibodies for serious diseases, including cancer. The company’s headquarters in Austin, Texas, houses its research, testing, and manufacturing facilities.