Trial Title:
Study of HRO761 Alone or in Combination in Cancer Patients With Specific DNA Alterations Called Microsatellite Instability or Mismatch Repair Deficiency.
NCT ID:
NCT05838768
Condition:
MSIhi or dMMR Advanced Unresectable or Metastatic Solid Tumors, Including Colorectal Cancers
Conditions: Official terms:
Colorectal Neoplasms
Microsatellite Instability
Pembrolizumab
Irinotecan
Conditions: Keywords:
Phase I/Ib
MSIhi (Microsatellite Instability-High)
dMMR (Mismatch Repair Deficient)
solid tumors
CRC (Colorectal cancer)
advanced cancer
metastatic
HRO761
pembrolizumab
irinotecan
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
This is an open label study. Treatment will be open to patients, Investigator staff,
persons performing the assessments and the Sponsor clinical trial team.
For the dose escalation and dose expansion, no randomization will be performed. For the
dose optimization (HRO761 single agent arm only), patients will be equally randomized to
the two selected HRO761 single agent treatment dose levels.
Intervention:
Intervention type:
Drug
Intervention name:
HRO761
Description:
Tablet
Arm group label:
A: HRO761 single agent
Arm group label:
B: HRO761 + pembrolizumab
Arm group label:
C: HRO761 + irinotecan
Intervention type:
Biological
Intervention name:
pembrolizumab
Description:
Concentrate for solution for infusion
Arm group label:
B: HRO761 + pembrolizumab
Intervention type:
Drug
Intervention name:
irinotecan
Description:
Concentrate for solution for infusion
Arm group label:
C: HRO761 + irinotecan
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 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.
Detailed description:
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 pembrolizumab or irinotecan.
Pembrolizumab and irinotecan are drugs approved in several countries and 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 HRO761 with pembrolizumab or irinotecan also will 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 pembrolizumab 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.
Criteria for eligibility:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Of California LA Dept of Onc
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lisa Zhou
Phone:
310-582-4069
Email:
LisaZhou@mednet.ucla.edu
Investigator:
Last name:
Zev A Wainberg
Email:
Principal Investigator
Facility:
Name:
UCSF
Address:
City:
San Francisco
Zip:
94115
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rachel Sanyu
Phone:
415-353-7284
Email:
Rachel.Sanyu@ucsf.edu
Investigator:
Last name:
Pamela Munster
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Dept. of MSKCC
Address:
City:
New York
Zip:
10017
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jill Weiss
Phone:
+1 646 227 2157
Email:
weissj2@mskcc.org
Investigator:
Last name:
Michael Bonner Foote
Email:
Principal Investigator
Facility:
Name:
Columbia University Medical Ctr .
Address:
City:
New York
Zip:
10032
Country:
United States
Status:
Recruiting
Contact:
Last name:
Joy Kim
Phone:
646-317-4850
Email:
jk4704@cumc.columbia.edu
Investigator:
Last name:
Edmond Chan
Email:
Principal Investigator
Facility:
Name:
Univ of TX MD Anderson Cancer Cntr Primary
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Timothy Yap
Email:
Principal Investigator
Facility:
Name:
Novartis Investigative Site
Address:
City:
Bruxelles
Zip:
1200
Country:
Belgium
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Beijing
Zip:
100036
Country:
China
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Marseille
Zip:
13273
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Essen
Zip:
45147
Country:
Germany
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Ulm
Zip:
89081
Country:
Germany
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Tel Aviv
Zip:
6423906
Country:
Israel
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Milano
Zip:
20162
Country:
Italy
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Rozzano
Zip:
20089
Country:
Italy
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Kashiwa
Zip:
277 8577
Country:
Japan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Seoul
Zip:
03722
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Oslo
Zip:
NO-0379
Country:
Norway
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Singapore
Zip:
119228
Country:
Singapore
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Madrid
Zip:
28009
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Stockholm
Zip:
17176
Country:
Sweden
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Taipei
Zip:
10002
Country:
Taiwan
Status:
Recruiting
Start date:
June 27, 2023
Completion date:
January 31, 2030
Lead sponsor:
Agency:
Novartis Pharmaceuticals
Agency class:
Industry
Source:
Novartis
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05838768
