Treatment of Cabotamig (ARB202) in Advanced Gastrointestinal Cancer Patients

Arbele

Status and phase: Enrolling; Phase 1

Conditions: Colorectal Adenocarcinoma; Gastric Cancer; Gastrointestinal Cancer; Cholangiocarcinoma; Esophageal Adenocarcinoma; Liver Cancer; Gastroesophageal Junction; Pancreatic Cancer

Treatments: Drug: Cabotamig (ARB202)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05411133

A001

Details and patient eligibility

About

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.

Enrollment: 68 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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68 participants in 5 patient groups

Phase 1a: Dose Escalation

Experimental group

Treatment:

Drug: Cabotamig (ARB202)

Phase 1b: Low dose Cabotamig (ARB202)

Experimental group

Treatment:

Drug: Cabotamig (ARB202)

Phase 1b: High dose Cabotamig (ARB202)

Experimental group

Treatment:

Drug: Cabotamig (ARB202)

Phase 1b: Low dose Cabotamig (ARB202) + Immune Checkpoint Inhibitor

Experimental group

Treatment:

Drug: Cabotamig (ARB202)

Phase 1b: High dose Cabotamig (ARB202) + Immune Checkpoint Inhibitor

Experimental group

Treatment:

Drug: Cabotamig (ARB202)