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Testing HRO761 for cancer patients with specific DNA alterations

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.

Phase 1 Interventional Novartis · NCT05838768

This study is testing a new oral drug called HRO761 to see if it can help cancer patients with certain DNA changes feel better and improve their treatment options.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment327 (estimated)
Ages18 Years to 100 Years
SexAll
SponsorNovartis Industry-sponsored
Drugs / interventionschemotherapy, pembrolizumab
Locations28 sites (Los Angeles, California and 27 other locations)
Trial IDNCT05838768 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and tolerability of HRO761, an oral drug targeting the Werner protein, in patients with advanced unresectable or metastatic solid tumors characterized by microsatellite instability-high (MSIhi) or mismatch repair deficiency (dMMR). The trial consists of multiple treatment arms, including HRO761 alone and in combination with pembrolizumab or irinotecan. It aims to determine the optimal safe and active doses through a dose escalation and optimization approach. The study will also assess the effectiveness of HRO761 in treating these specific cancer types.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced unresectable or metastatic MSIhi or dMMR solid tumors who have progressed after or are intolerant to prior standard therapy.

Not a fit: Patients with solid tumors that do not exhibit MSIhi or dMMR characteristics may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with difficult-to-treat cancers characterized by specific DNA alterations.

How similar studies have performed: While this approach is novel in using HRO761, similar studies with other drugs targeting MSIhi or dMMR tumors have shown promising results.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion criteria:

* Patients with advanced unresectable or metastatic MSIhi or MMR deficient (dMMR) solid tumors who have progressed after or are intolerant to prior standard therapy.

  * Arm A and C: Patients must have progressed on the most recent therapy for advanced disease including one prior line of immune checkpoint inhibitor therapy.
  * Arm B: Patients should have received prior chemotherapy or targeted therapy, and patients should have received prior immune checkpoint inhibitor or should be expected to benefit from immune checkpoint inhibitor therapy.
* Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
* Measurable disease as determined by RECIST version 1.1
* HRO761 s.a. (Arm A) dose finding only: Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patients must be willing to undergo a new tumor biopsy at screening, and during therapy on the study. A biopsy from the same lesion is preferred if safe and medically feasible. Exceptions may be considered after documented discussion with Novartis.
* All patients (Arm A, B and C) will have available archival tumor tissue obtained prior to study treatment initiation (in addition to newly obtained tumor biopsy at screening for Arm A), to allow retrospective MSIhi/dMMR status confirmation.

Key Exclusion criteria:

* Impaired cardiac function or clinically significant cardiac disease
* Clinically significant eye impairment
* Patients with a primary Central Nervous System (CNS) tumor or tumor metastatic to the CNS
* Human Immunodeficiency Virus (HIV) infection
* Active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Tuberculosis infection. Patients whose disease is controlled under antiviral therapy should not be excluded.
* History of severe hypersensitivity reactions to any ingredient of study drug(s)
* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., severe ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection), except for prior gastrectomy.

Other protocol-defined inclusion/exclusion criteria may apply

Where this trial is running

Los Angeles, California and 27 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions MSIhi or dMMR Advanced Unresectable or Metastatic Solid Tumors, Including Colorectal CancersPhase I/IbMSIhidMMRsolid tumorsCRCadvanced cancermetastatic
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.