A Study of exoASO-STAT6 (CDK-004) in Patients With Advanced Hepatocellular Carcinoma (HCC) and Patients With Liver Metastases From Primary Gastric Cancer and Colorectal Cancer (CRC)

Sponsor

Codiak BioSciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05375604

Collaborator

(none)

Enrollment

Locations

Arm

23.5

Anticipated Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a first-in-human, Phase 1 open-label, multicenter, dose escalation, safety, pharmacodynamic, and PK study of exoASO-STAT6 (CDK-004) in patients with advanced Hepatocellular Carcinoma (HCC) and patients with liver metastases from primary gastric cancer and colorectal cancer (CRC).

Condition or Disease	Intervention/Treatment	Phase
Advanced Hepatocellular Carcinoma (HCC) Gastric Cancer Metastatic to Liver Colorectal Cancer Metastatic to Liver	Drug: CDK-004	Phase 1

Detailed Description

CDK-004 as an intravenous (IV) treatment for advanced hepatocellular carcinoma (HCC), and primary gastric cancer and CRC with secondary liver metastases.

CDK-004 is an investigational therapeutic candidate consisting of cell-derived exosomes loaded with a synthetic lipid-tagged oligonucleotide.

CDK-004 is designed to allow for specific delivery of the STAT6 anti-sense oligonucleotide (ASO) to the myloid to repolarize macrophage from immune suppressive M2 to proinflammatory M1 phenotype, with a potential for meaningful single agent antitumor activity which has not been observed with other pathway inhibitors to date.

CDK-004 will be administered as a single agent intravenously (IV) at various doses.

Dose limiting toxicities (DLTs) will be assessed during the study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1 Study of Macrophage Reprogramming Agent, exoASO-STAT6 (CDK-004), in Patients With Advanced Hepatocellular Carcinoma (HCC) and Patients With Liver Metastases From Primary Gastric Cancer and Colorectal Cancer (CRC)

Anticipated Study Start Date :

May 16, 2022

Anticipated Primary Completion Date :

Oct 31, 2023

Anticipated Study Completion Date :

Apr 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Other: Experimental CDK-004	Drug: CDK-004 ASO-STAT6 exosome administered Intravenously Other Names: exoASO-STAT6

Arm

Intervention/Treatment

Other: Experimental CDK-004

Drug: CDK-004

ASO-STAT6 exosome administered Intravenously

Other Names:

exoASO-STAT6

Outcome Measures

Primary Outcome Measures

To characterize the safety and tolerability of CDK-004. [Up to 2 years]
Incidence of treatment-emergent adverse events as assessed by CTCAE 5.0.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must have one of the following cancer types:
Advanced HCC defined as Barcelona Clinic Liver Cancer (BCLC) Stage B/C not amenable to resection or locoregional therapy;
Histologic or radiologic proof of liver metastasis from primary CRC which is unresectable with no evidence of extrahepatic metastasis;
Histologic or radiologic proof of liver metastasis from primary gastric cancer which is unresectable with no evidence of extrahepatic metastasis.
Documented progression after at least 1 line of FDA approved systemic therapy for advanced HCC/gastric cancer/CRC or intolerable/refuse to chemotherapy.
≥ 18 years of age at screening.
Measurable disease by RECIST v1.1.
Willingness to provide archival tumor tissue (if available) and to undergo pre- and on-treatment tumor biopsies if considered safe and medically feasible by the Investigator.
ECOG performance status of 0-2.
Acceptable liver function
Acceptable renal function
Acceptable hematologic status
Cirrhosis classified as Child-Pugh Class A.
Women of child-bearing potential agree to use highly effective contraceptive methods and avoid egg donation and preservation during the study treatment and for 6 months after the last dose of study drug.
Men of child-producing potential agree to use highly effective contraceptive methods and avoid sperm donation and preservation during the study treatment and for 6 months after the last dose of study drug.

Exclusion Criteria:

Treatment with any systemic or liver-directed anticancer therapy within 3 weeks of the first dose of study drug.
Uncontrolled partial or complete biliary obstruction.
Left ventricular ejection fraction (LVEF) < 50% at Screening.
12-lead ECG demonstrating QT interval corrected by Fridericia's formula (QTcF) > 480 ms or history of long QTc syndrome.
Ongoing, clinically significant AEs due to prior anticancer therapies.
Patients with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present or in the opinion of the Investigator will not affect patient outcome.
Known clinically active brain metastases or known carcinomatous meningitis/leptomeningeal disease.
Known clinically significant infection.
Known clinically significant cardiac disease, including unstable angina or has had a procedure to address the underlying cause and has experienced angina within 4 weeks prior to Cycle 1 Day 1, acute myocardial infarction within 6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure.
Known history of human immunodeficiency virus (HIV).
If history of concurrent Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection, meets the following criteria: patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should be managed per local treatment guidelines. Controlled (treated) hepatitis B patients will be allowed if they started treatment at the time of consent and treatment is continued during study participation; patients with hepatitis C and detectable RNA are eligible if antiviral therapy has been completed prior to first administration of study drug. Testing does not need to be conducted at Screening if results from testing within the past 12 months are available.
History of liver transplant.
History of immunodeficiency or is receiving chronic systemic steroid therapy
Poorly controlled diabetes mellitus.
Active or previously documented autoimmune or inflammatory diseases
Is currently participating in a study of an investigational therapy or device or has participated and received an investigation therapy or device within 3 weeks of administration of CDK-004.
Has another physical or mental health disorder that might cause difficulty in obtaining informed consent and/or participation in the trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
3	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203