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.

Study Identifier:
CHRO761A12101
CT.gov Identifier:
NCT05838768
EudraCT Identifier:
202250000000
EU Trial (CTIS) Number:
2022-502314-93-00
Study Contact Information:
N/A
Recruitment Complete

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Study Summary

To evaluate the safety and tolerability of HRO761 and identify the recommended dose(s), i.e., the optimal safe and active dose of HRO761 alone or in combination with tislelizumab or irinotecan that can be given to patients who have cancers with specific molecular alterations called MSIhi (Microsatellite Instability-high) or dMMR (Mismatch Repair Deficient) that might work best to treat these specific cancer types and to understand how well HRO761 is able to treat those cancers.

To assess the safety, tolerability and preliminary anti-tumor activity in patients with MSI colorectal cancer and other MSI solid tumors.

To investigate HRO761 in pts with MSI-H/dMMR advanced solid tumors.

Key aims are to assess the safety/tolerability, recommended dose, and antitumor activity of HRO761.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
  • Bowel (Colorectal)
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18 - 100 Years
    Study Drug
  • Drug: Experimental: A: HRO761 single agent
    • Read More
  • Drug: Experimental: B: HRO761 + pembrolizumab
  • Drug: Biological: pembrolizumab
  • Drug: Experimental: C: HRO761 + irinotecan
  • Drug: Drug: irinotecan
  • Drug: Experimental drug
  • Drug: HRO761 was administered either once or twice daily at a total daily dose of 100-900 mg.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    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
    • • All patients (Arm A, B and C) will have available archival tumor tissue obtained prior to study treatment initiation, to allow retrospective MSIhi/dMMR status confirmation. A newly obtained biopsy will only be collected at screening if there is no archival tumor tissue available and if safe and medically feasible according to treating institution's guidelines. Exceptions may be considered after documented discussion with Novartis.
    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

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Solid Tumor
    Bowel (Colorectal)