Clinical trial NCT05411133: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Gastrointestinal Cancer
Cholangiocarcinoma
Liver Cancer
Colorectal Adenocarcinoma
Pancreatic Cancer
Gastric Cancer
Esophageal Adenocarcinoma
Gastroesophageal Junction
Lead sponsor: Arbele Limited
Sponsor class: INDUSTRY
First posted: 2022-06-09
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: 8 weeks post initial dose
Secondary outcomes:
measure: Amount of Cabotamig (ARB202) in plasma after single and multiple doses of ARB202 (Cabotamig) in patients
timeFrame: 16 weeks
measure: Biochemical and physiological effects of Cabotamig (ARB202) on the amount of circulating ARB202 (Cabotamig) level in patients
timeFrame: 16 weeks
measure: Biochemical and physiological effects of Cabotamig (ARB202) on the amount of soluble CDH17 level in patients
timeFrame: 16 weeks
measure: Biochemical and physiological effects of Cabotamig (ARB202) on the amount IL-2 level in patients
timeFrame: 16 weeks
measure: Effect of Cabotamig (ARB202) on tumour as determined by changes in RECIST evaluation from baseline
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Southern Oncology Clinical Research Unit
city: Sydney
country: Australia
facility: St George Private Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
Study officials:
References: