- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05838768
Study of HRO761 Alone or in Combination in Cancer Patients With Specific DNA Alterations Called Microsatellite Instability or Mismatch Repair Deficiency.
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 Overview
Status
Conditions
Intervention / Treatment
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 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.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Novartis Pharmaceuticals
- Phone Number: 1-888-669-6682
- Email: novartis.email@novartis.com
Study Contact Backup
- Name: Novartis Pharmaceuticals
- Phone Number: +41613241111
Study Locations
-
-
-
Bruxelles, Belgium, 1200
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Bordeaux, France, 33076
- Recruiting
- Novartis Investigative Site
-
Marseille, France, 13273
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Essen, Germany, 45147
- Recruiting
- Novartis Investigative Site
-
Ulm, Germany, 89081
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Tel Aviv, Israel, 6423906
- Recruiting
- Novartis Investigative Site
-
-
-
-
Chiba
-
Kashiwa, Chiba, Japan, 277 8577
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Seoul, Korea, Republic of, 03722
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Singapore, Singapore, 119228
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Madrid, Spain, 28009
- Recruiting
- Novartis Investigative Site
-
-
Comunidad Valenciana
-
Valencia, Comunidad Valenciana, Spain, 46010
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Taipei, Taiwan, 10002
- Recruiting
- Novartis Investigative Site
-
-
-
-
California
-
Los Angeles, California, United States, 90095
- Recruiting
- University Of California LA Dept of Onc
-
Principal Investigator:
- Zev A Wainberg
-
Contact:
- Lisa Zhou
- Phone Number: 310-582-4069
- Email: LisaZhou@mednet.ucla.edu
-
-
New York
-
New York, New York, United States, 10017
- Recruiting
- Memorial Sloan Kettering Dept. of MSKCC
-
Principal Investigator:
- Michael Bonner Foote
-
Contact:
- Jill Weiss
- Phone Number: +1 646 227 2157
- Email: weissj2@mskcc.org
-
New York, New York, United States, 10032
- Recruiting
- Columbia University Medical Ctr .
-
Principal Investigator:
- Edmond Chan
-
Contact:
- Joy Kim
- Phone Number: 646-317-4850
- Email: jk4704@cumc.columbia.edu
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- Univ of TX MD Anderson Cancer Cntr Primary
-
Principal Investigator:
- Timothy Yap
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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 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.
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: A: HRO761 single agent
phase Ib (Dose finding (Escalation and Optimization) and expansion)
|
Tablet
|
Experimental: B: HRO761 + tislelizumab
phase Ib (Dose escalation and expansion)
|
Tablet
Concentrate for solution for infusion
Other Names:
|
Experimental: C: HRO761 + irinotecan
phase Ib (Dose escalation and expansion)
|
Tablet
Concentrate for solution for infusion
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: at month 36
|
Month 36 is assumed to be study end. Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs. |
at month 36
|
Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only)
Time Frame: at Day 28
|
A DLT is defined as an adverse event or abnormal laboratory value that is not primarily related to disease, disease progression, intercurrent illness/injury, or concomitant medications that occurs within the first 28 days of study treatment and meets a defined criteria.
|
at Day 28
|
Frequency of dose interuptions as a measure of tolerability
Time Frame: at month 36
|
Month 36 is assumed to be study end Number of dose interruptions by treatment group/arm as a measure of tolerability. |
at month 36
|
Frequency of dose discontinuations as a measure of tolerability
Time Frame: at month 36
|
Month 36 is assumed to be study end Number of dose discontinuations by treatment group/arm as a measure of tolerability. |
at month 36
|
Frequency of dose reductions as a measure of tolerability
Time Frame: at month 36
|
Month 36 is assumed to be study end Number of dose reductions by treatment group/arm as a measure of tolerability. |
at month 36
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR) per RECIST v1.1
Time Frame: at month 36
|
Month 36 is assumed to be study end ORR is the percentage of patients with a best overall response of Complete Response (CR) or Partial Response (PR). |
at month 36
|
Disease Control Rate (DCR) per RECIST v1.1
Time Frame: at month 36
|
Month 36 is assumed to be study end DCR is the percentage of patients with a best overall response of CR or PR or Stable Disease (SD) |
at month 36
|
Progression Free Survival (PFS) per RECIST v1.1
Time Frame: at month 36
|
Month 36 is assumed to be study end PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. |
at month 36
|
Duration of Response (DOR) per RECIST v1.1
Time Frame: at month 36
|
Month 36 is assumed to be study end DOR is the time between the date of first documented response (CR or PR) and the date of progression or death due to any cause. |
at month 36
|
Plasma concentrations of HRO761
Time Frame: at Day 1, Day 8, Day 29, Day 57, Day 85, Day 113, Day 141, Day 225, Day 309 and EOT
|
Plasma concentrations of HRO761 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay.
|
at Day 1, Day 8, Day 29, Day 57, Day 85, Day 113, Day 141, Day 225, Day 309 and EOT
|
PK parameter (Tmax) of HRO761
Time Frame: at month 12
|
Cycle 12 (the duration of 1 cycle is 28 days). Time to maximum observed concentration (Tmax) determined by non-compartmental PK analysis of plasma concentration-time profiles HRO761. |
at month 12
|
PK parameter (Cmax) of HRO761
Time Frame: at month 12
|
Cycle 12 (the duration of 1 cycle is 28 days). Maximum observed concentration (Cmax) determined by non-compartmental pharmacokinetic (PK) analysis of plasma concentration-time profiles HRO761. |
at month 12
|
PK parameter (AUC) of HRO761
Time Frame: at month 12
|
Cycle 12 (the duration of 1 cycle is 28 days). Area under the plasma concentration-time curve (AUC) determined by non-compartmental PK analysis of plasma concentration-time profiles HRO761. |
at month 12
|
Serum concentrations of tislelizumab
Time Frame: at Day 1, Day 8, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 225, Day 309 and EOT
|
Serum concentrations of tislelizumab will be measured using a validated immunoassay
|
at Day 1, Day 8, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 225, Day 309 and EOT
|
PK parameter (Tmax) of tislelizumab
Time Frame: at month 12
|
Cycle 12 (the duration of 1 cycle is 28 days). Tmax determined by non-compartmental PK analysis of serum concentration-time profiles tislelizumab. |
at month 12
|
PK parameter (Cmax) of tislelizumab
Time Frame: at month 12
|
Cycle 12 (the duration of 1 cycle is 28 days). Cmax determined by non-compartmental PK analysis of serum concentration-time profiles tislelizumab. |
at month 12
|
PK parameter (AUC) of tislelizumab
Time Frame: at month 12
|
Cycle 12 (the duration of 1 cycle is 28 days). AUC determined by non-compartmental PK analysis of plasma concentration-time profiles tislelizumab. |
at month 12
|
Number of participants with anti tislelizumab antibodies
Time Frame: Up to 36 months
|
Anti-tislelizumab antibodies determined from serum using validated Enzyme-Linked Immunosorbent Assay (ELISA).
|
Up to 36 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Genomic Instability
- Colorectal Neoplasms
- Microsatellite Instability
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Topoisomerase I Inhibitors
- Irinotecan
- Tislelizumab
Other Study ID Numbers
- CHRO761A12101
- 2022-502314-93-00 (Registry Identifier: EU CTIS)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on MSIhi or dMMR Advanced Unresectable or Metastatic Solid Tumors, Including Colorectal Cancers
-
Zhejiang UniversityNot yet recruitingUnresectable or Metastatic Advanced Solid Tumors
-
EMD Serono Research & Development Institute, Inc.Merck KGaA, Darmstadt, GermanyTerminatedMetastatic or Locally Advanced Unresectable Solid TumorsUnited States
-
Hangzhou Sumgen Biotech Co., Ltd.RecruitingLocally Advanced Unresectable or Metastatic Solid TumorsChina
-
EMD Serono Research & Development Institute, Inc.Merck KGaA, Darmstadt, GermanyActive, not recruitingMetastatic or Locally Advanced Unresectable Solid TumorsUnited States, China, Spain, Japan, United Kingdom
-
EMD Serono Research & Development Institute, Inc.Merck KGaA, Darmstadt, GermanyTerminatedMetastatic or Locally Advanced Unresectable Solid TumorsUnited States, Canada
-
Innovent Biologics (Suzhou) Co. Ltd.RecruitingLocally Advanced Unresectable or Metastatic Solid TumorsAustralia
-
Innovent Biologics (Suzhou) Co. Ltd.RecruitingLocally Advanced Unresectable or Metastatic Solid TumorsAustralia
-
EMD Serono Research & Development Institute, Inc.Merck KGaA, Darmstadt, GermanyRecruitingMetastatic or Locally Advanced Unresectable Solid TumorsUnited States, Canada, Spain
-
Txinno Bioscience Inc.RecruitingLocally Advanced (Unresectable) or Metastatic Solid TumorsKorea, Republic of
-
Innovent Biologics (Suzhou) Co. Ltd.Not yet recruitingLocally Advanced Unresectable or Metastatic Solid TumorsAustralia