Active Cancer NIHR-supported project Digestion, Kidneys & Other Organs

An open-label, multi-center phase I/Ib dose finding and expansion study of HRO761 as single agent and in combinations in patients with Microsatellite Instability-High or Mismatch Repair Deficient advanced solid tumors

Funder NIHR (part of DHSC)
Recipient organisation NIHR Royal Marsden Clinical Research Facility
NIHR support Recorded as supported by this research centre
Period Mar 2025 — Aug 2026

In plain English

AI plain-English summary

A new drug called HRO761 is being tested in patients with advanced cancers that have specific DNA repair defects, to find a safe dose and see if it can shrink tumours. These cancers—marked by high microsatellite instability (MSIhi) or mismatch repair deficiency (dMMR)—are often resistant to standard treatments. HRO761 targets the Werner protein (WRN), which these cancer cells rely on to survive. By blocking WRN, the drug aims to selectively kill tumour cells while sparing healthy tissue. The trial also tests HRO761 combined with either the immunotherapy tislelizumab or the chemotherapy irinotecan. If successful, this research could offer a new treatment option for patients with MSIhi or dMMR solid tumours who have run out of effective therapies. That includes people with colorectal, endometrial, gastric, and other cancers where these defects are common. The trial is open-label, meaning everyone knows which treatment each patient receives. It proceeds in two phases: first, dose-finding in small groups; then, expansion to more patients at the safe dose to assess anti-tumour activity across different cancer types.

View original technical description
The main purpose of the study is to find the safe dose of HRO761 alone or in combination with tislelizumab or irinotecan, also called study treatments. HRO761 acts on a protein called Werner (WRN), which may contribute to cancer growth. By acting on WRN, HRO761 may be able to stop the growth of the cancers with defects called MSIhi (Microsatellite Instability-high) or dMMR (Mismatch Repair Deficient). This trial is designed to learn about the safety of the HRO761, and when combined with tislelizumab or irinotecan. This trial will find out how the body processes the study treatments, how the study treatments interact with the body as well as find out how well HRO761 alone or in combination with tislelizumab or irinotecan can treat those cancers.The patient, the trial doctor, and Novartis will know the study treatment which is being given to each patient. There are two parts in this study. During part one, different groups of patients will be given different doses of HRO761 alone or in combination with either tislelizumab or irinotecan until the safe dose is found. In part two, more patients will be treated with the safe dose of HRO761 alone or in combination with either tislelizumab or irinotecan to further assess the study treatment effects against various types of MSIhi or dMMR cancers. Trial participation will last until the patient’s disease worsens, their doctor decides they should no longer participate in the trial, or the patient does not want to further participate in the trial.Trial population:(1) Adult patients with cancers that have defects called MSIhi or dMMR. Patients must have previously received other treatments but are no longer benefiting from them. (2) The cancer must be measurable. (3) Patients must be willing to have a biopsy of the cancer before receiving and during trial treatment. (4) Patients must not have significant heart disease, (5) must not have significant eye disorders, (6) must not have an active, serious infection.

Researchers

Naureen Starling (Principal Investigator)

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