Study of HRO761 Alone or in Combination in Cancer Patients With Specific DNA Alterations Called Microsatellite Instability or Mismatch Repair Deficiency.

NCT05838768 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CHRO761A121012022-502314-93-00
• Study Type: interventional
• Target: 123
• Locations: 15 countries
• Sites: 28

Brief 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.

Conditions

MSIhi or dMMR Advanced Unresectable or Metastatic Solid Tumors, Including Colorectal Cancers

Keywords

Phase I/Ib; MSIhi (Microsatellite Instability-High); dMMR (Mismatch Repair Deficient); solid tumors; CRC (Colorectal cancer); advanced cancer; metastatic; HRO761; pembrolizumab; irinotecan

Outcome Measures

Primary Outcomes (5)

• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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)

  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

  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

  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

  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 Outcomes (8)

• Overall Response Rate (ORR) per RECIST v1.1

  at month 36

• Disease Control Rate (DCR) per RECIST v1.1

  at month 36

• Progression Free Survival (PFS) per RECIST v1.1

  at month 36

• Duration of Response (DOR) per RECIST v1.1

  at month 36

• Plasma concentrations of HRO761

  at Day 1, Day 8, Day 29, Day 57, Day 85, Day 113, Day 141, Day 225, and Day 309

Study Arms (3)

A: HRO761 single agent

EXPERIMENTAL

phase Ib (Dose finding (Escalation and Optimization) and expansion)

Drug: HRO761

B: HRO761 + pembrolizumab

EXPERIMENTAL

phase Ib (Dose escalation and expansion)

Drug: HRO761; Biological: pembrolizumab

C: HRO761 + irinotecan

EXPERIMENTAL

phase Ib (Dose escalation and expansion)

Drug: HRO761; Drug: irinotecan

Interventions

HRO761 DRUG

Tablet

A: HRO761 single agent; B: HRO761 + pembrolizumab; C: HRO761 + irinotecan

pembrolizumab BIOLOGICAL

Concentrate for solution for infusion

B: HRO761 + pembrolizumab

irinotecan DRUG

Concentrate for solution for infusion

C: HRO761 + irinotecan

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (28)

University of California LA

Los Angeles, California, 90095, United States

Location

UCSF

San Francisco, California, 94115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering

New York, New York, 10017, United States

Location

Columbia University Medical Ctr

New York, New York, 10032, United States

Location

Univ of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Guangzhou, 510655, China

Location

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Kashiwa, Chiba, 2778577, Japan

Location

Novartis Investigative Site

Oslo, 0310, Norway

Location

Novartis Investigative Site

Singapore, 119228, Singapore

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Valencia, 46010, Spain

Location

Novartis Investigative Site

Stockholm, 17176, Sweden

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

London, SW3 6JJ, United Kingdom

Location

Novartis Investigative Site

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Turcot syndrome; Colorectal Neoplasms; Neoplasm Metastasis

Interventions

pembrolizumab; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2023
• First Posted: May 3, 2023
• Study Start: June 27, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); DE (1); CN (2); KR (1); BE (1); JP (1); IT (2); NO (1); SE (1); SG (1); TW (1); GB (2); ES (4); US (6); IL (1)