Novartis Presents First-in-Class WRN Inhibitor HRO761 with Promising Phase I/Ib Clinical Data in MSI-H/dMMR Solid Tumors at ESMO 2025
Novartis
Drug Development and Manufacturing
On October 13 local time, the main text of the regular abstracts for the 2025 ESMO Annual Meeting was重磅 released. At this conference, Novartis disclosed through a mini oral presentationHRO761 First-in-Human Phase I/Ib StudyInterim Results of Single-Agent Dose Escalation.
Screenshot source: ESMO official website
HRO761 is aFirst-in-class, efficient, selective WRN inhibitor, previous research has suggested thatWRN Inhibitors May Provide New Treatment Avenues for MSI-High Cancers.
The following is aOpen, Multi-center, Phase I/Ib Dose Exploration and Expansion Study，Aim to study HRO761 treatmentMSI-H/dMMR Advanced Solid TumorsThe patient's efficacy.
As of February 12, 2025, a total of 47 patients have been enrolled.（Progression or intolerance after receiving prior standard treatments, including the need for immune checkpoint inhibitor therapy.），The median number of prior treatment lines was 4, including 27 patients with colorectal cancer. (CRC) Patient.
The results showed,35 cases after baseline（BL）Scanned patients,The overall response rate was 8.6%.(19 cases of CRC patients accounted for 10.5%)，The disease control rate was 68.6%.(CRC patients accounted for 84.2%)，Median PFS was 5.6 months. Daily dose of 200 milligrams(10 patients)，The PFS rate at 9 months was 68.6%. (95% CI 30.5, 88.7)。
BL circulating tumor DNA detectable(ctDNA) In patients,1/1 patient had ctDNA cleared within approximately 1 month, partial response; 5/8 patients had stable disease.，0/5 cases of disease progression; 6 patients with ctDNA clearance(Among them, 5 cases are still under treatment)OfThe median treatment duration was 9.3 months.。
Screenshot source: ESMO official website
HRO761 exposure is almost dose-linear, with an accumulation of approximately 2-fold. 28 patients(59.6%) Reported treatment-related adverse events (TRAE); The most common adverse event was nausea.(10 patients, 21.3%)、Diarrhea(6 patients, 12.8%)And vomiting(5 patients, 10.6%), and all were grade 1/2. (G). 5 patients (10.6%) Reported G3 TRAE, 3 patients(6.4%)Reported serious TRAE; no G4/5 TRAE was reported.
Overall, HRO761 in patients receiving extensive treatmentImmune Checkpoint InhibitorsMSI-H/dMMR cancer patients in the later stages exhibitedAcceptable safety and durable anti-tumor activity, and can eliminate ctDNA.
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