Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
completion around
Principal Investigator
by Zev A Wainberg (ucla)

Description

Summary

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 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.

Official Title

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.

Details

The new drug being tested in the study, HRO761, is an oral drug that 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 cancer.

This is the first time HRO761 is given to patients and the first time HRO761 is used in combination with tislelizumab or irinotecan.

Tislelizumab has been used in other cancer studies in the past few years and irinotecan is a drug approved in several countries and is used as standard treatment for certain types of cancer (e.g., colon cancer and small cell lung cancer).

This research study will consist of various treatment arms to investigate HRO761 as single agent and in the combinations.

For HRO761 single agent, the research will be done in two parts the first part is called "dose escalation" and the second part is called "dose optimization" In the dose escalation part, different groups of people will be given different doses of HRO761 to understand how the body reacts to different doses of the drug and how well the drug acts against the cancer. During the dose optimization part, the selected doses will be tested in more patients until a recommended dose(s) is found.

The combinations of HRO761with tislelizumab or irinotecan will also first be tested in a dose escalation part to find the recommended doses of HRO761 in these combinations.

Once the recommended doses are determined, more people may be treated with HRO761 alone or together with tislelizumab or irinotecan to further assess the study treatment effects against various types of MSIhi or dMMR cancers. This part is called dose expansion.

For this research, a number of blood and tissue samples will be collected during the study. Patients may be asked to come approximately 8 times to the clinic during the first 8 weeks and approximately every 2 or 4 weeks thereafter.

Patients will be in the study as long as their study doctor believes that they may be benefiting from the study treatment, unless the patient decides to stop study treatment.

Keywords

MSIhi or dMMR Advanced Unresectable or Metastatic Solid Tumors, Including Colorectal Cancers, Phase I/Ib, MSIhi (Microsatellite Instability-High), dMMR (Mismatch Repair Deficient), solid tumors, CRC (Colorectal cancer), advanced cancer, metastatic, HRO761, tislelizumab, irinotecan, Colorectal Neoplasms, Microsatellite Instability, A: HRO761 single agent, B: HRO761 + tislelizumab, C: HRO761 + irinotecan

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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 may have received prior chemotherapy or targeted therapy but should not have or without prior treatment with immune checkpoint inhibitors.
  • 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.

You CAN'T join if...

  • 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

Locations

  • University Of California LA Dept of Onc accepting new patients
    Los Angeles California 90095 United States
  • Univ of TX MD Anderson Cancer Cntr Primary accepting new patients
    Houston Texas 77030 United States

Lead Scientist at University of California Health

  • Zev A Wainberg (ucla)
    HS Clinical Professor, Medicine. Authored (or co-authored) 153 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
ID
NCT05838768
Phase
Phase 1 research study
Study Type
Interventional
Participants
Expecting 327 study participants
Last Updated