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Study of HRO761 Alone or in Combination in Cancer Patients With Specific DNA Alterations Called Microsatellite Instability or Mismatch Repair Deficiency.
Trial Status: active
The main purpose of the study is 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 pembrolizumab 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.
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
Additional locations may be listed on ClinicalTrials.gov for NCT05838768.
