Treatment of Cabotamig (ARB202) in Advanced Gastrointestinal Cancer Patients

• ClinicalTrials.gov Identifier: NCT05411133
• Recruitment Status: Recruiting
• First Posted: June 9, 2022
• Last Update Posted: January 23, 2024
• Sponsor: Arbele Pty Ltd
• Information provided by (Responsible Party): Arbele Limited ( Arbele Pty Ltd )

Tracking Information

• First Submitted Date: May 25, 2022
• First Posted Date: June 9, 2022
• Last Update Posted Date: January 23, 2024
• Actual Study Start Date: May 30, 2022
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 5, 2022): Incidence and severity of adverse events [ Time Frame: 8 weeks post initial dose ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 22, 2024)

• Amount of Cabotamig (ARB202) in plasma after single and multiple doses of ARB202 (Cabotamig) in patients [ Time Frame: 16 weeks ]
• Biochemical and physiological effects of Cabotamig (ARB202) on the amount of circulating ARB202 (Cabotamig) level in patients [ Time Frame: 16 weeks ]
• Biochemical and physiological effects of Cabotamig (ARB202) on the amount of soluble CDH17 level in patients [ Time Frame: 16 weeks ]
• Biochemical and physiological effects of Cabotamig (ARB202) on the amount IL-2 level in patients [ Time Frame: 16 weeks ]
• Effect of Cabotamig (ARB202) on tumour as determined by changes in RECIST evaluation from baseline [ Time Frame: 6 weeks ]

Original Secondary Outcome Measures (submitted: June 5, 2022)

• Amount of ARB202 in plasma after single and multiple doses of ARB202 in patients [ Time Frame: 16 weeks ]
• Biochemical and physiological effects of ARB202 on the amount of circulating ARB202 level in patients [ Time Frame: 16 weeks ]
• Biochemical and physiological effects of ARB202 on the amount of soluble CDH17 level in patients [ Time Frame: 16 weeks ]
• Biochemical and physiological effects of ARB202 on the amount IL-2 level in patients [ Time Frame: 16 weeks ]
• Effect of ARB202 on tumour as determined by changes in RECIST evaluation from baseline [ Time Frame: 6 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Treatment of Cabotamig (ARB202) in Advanced Gastrointestinal Cancer Patients
• Official Title: A Phase 1, First-in-human Study of Cabotamig (ARB202), Bispecific Antibody to CDH17 and CD3 in Advanced Gastrointestinal Malignancies

Brief Summary

This study aims to find out:

1. The tolerability of Cabotamig (ARB202) in adults with advanced solid gastrointestinal tumors who failed the standard treatment. People can participate if their tumor has the CDH17 marker.
2. To find out how study drug is broken down in the body
3. To know the effects of the study drug on the tumor.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Gastrointestinal Cancer
• Cholangiocarcinoma
• Liver Cancer
• Colorectal Adenocarcinoma
• Pancreatic Cancer
• Gastric Cancer
• Esophageal Adenocarcinoma
• Gastroesophageal Junction

Intervention

Drug: Cabotamig (ARB202)

Cabotamig (ARB202), Atezolizumab

Study Arms

• Experimental: Phase 1a: Dose Escalation
  Intervention: Drug: Cabotamig (ARB202)
• Experimental: Phase 1b: Low dose Cabotamig (ARB202)
  Intervention: Drug: Cabotamig (ARB202)
• Experimental: Phase 1b: High dose Cabotamig (ARB202)
  Intervention: Drug: Cabotamig (ARB202)
• Experimental: Phase 1b: Low dose Cabotamig (ARB202) + Immune Checkpoint Inhibitor
  Intervention: Drug: Cabotamig (ARB202)
• Experimental: Phase 1b: High dose Cabotamig (ARB202) + Immune Checkpoint Inhibitor
  Intervention: Drug: Cabotamig (ARB202)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 5, 2022): 68
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2025
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed colorectal, pancreatic, gastric adenocarcinoma, primary liver cancer or metastatic liver disease, or cholangiocarcinoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Malignancies should possess with ≥10% expression of CDH17 confirmed by immunohistochemistry except for CRC patients.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Life expectancy > 3 months.
• Measurable disease as defined by RECIST 1.1 criteria

• Blood coagulation parameters:

  • PT INR ≤ 1.5X ULN
  • PTT INR ≤1.2X ULN
• Patients must have adequate venous peripheral access for apheresis.

• Satisfactory organ and bone marrow function as defined by:

  • absolute neutrophil count > 1,000/μL
  • platelets >100,000/μL
  • hemoglobin ≥9 g/dL
  • serum ALT and AST ≤ 3X ULN or AST and ALT ≤5X ULN, if liver function abnormalities are thought to be from underlying malignancy
  • total serum bilirubin ≤ 2X ULN
  • Creatinine <1.5X ULN
  • Stable amylase for 2 weeks

Exclusion Criteria:

• Prior gene therapy or therapy with any murine monoclonal antibodies or any murine containing product.
• Concurrent treatment with any anticancer agent including chemotherapy, hormonal therapy or radiation therapy. Must be 5 X half-life or 6 weeks (whichever is shorter) post dosing of previous cancer therapies.
• History of allergy or hypersensitivity to murine proteins or study product excipients
• Females who are pregnant, trying to become pregnant, or breastfeeding.
• Diagnosis of HIV or chronic active viral hepatitis (HBV, HCV, HIV).
• Active infection requiring systemic treatment.
• Active brain, leptomeningeal, or paraspinal metastases, except for asymptomatic metastases and are stable on a steroid dose of ≤ 10mg/day of prednisone or its equivalent for at least 14 days prior to the start of study interventions.
• Impaired cardiac function (AHA NY Heart Association Grade II-IV) or clinically significant cardiac disease.
• Lack of recovery of prior CTCAE Grade 3 or above adverse events due to earlier therapies.
• Chronic use of corticosteroids in excess of >10mg daily of prednisone or equivalent within 4 weeks prior to alopecia.
• Concomitant use of complementary or alternative medication or therapy such as Chinese herbal medicine.
• History of Crohn's disease, inflammatory bowel disease, or ulcerative colitis within the past 5 years
• Abnormal bowel function which would make assessment of bowel permeability difficult to access
• Major trauma or major surgery within 4 weeks prior to first dose of study drug

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Dennis Wong, M.D; +1 415 632 6596; dennis.wong@arbelebio.com

• Listed Location Countries: Australia, Hong Kong
• Removed Location Countries: Singapore

Administrative Information

• NCT Number: NCT05411133
• Other Study ID Numbers: A001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Arbele Limited ( Arbele Pty Ltd )
• Original Responsible Party: Same as current
• Current Study Sponsor: Arbele Pty Ltd
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Arbele Limited
• Verification Date: January 2024