KAT-101 in Subjects With Hepatocellular Carcinoma (HCC)

Hepatocellular Carcinoma Clinical Trial

Official title:

A Multi-center, Open-label, Phase 1/2a Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of KAT-101 in Subjects With HCC

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05603572
• Other study ID #: NLP-KAT-101
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 1, 2022
• Est. completion date: November 2025

Study information

• Verified date: November 2023
• Source: NewG Lab Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

NLP-KAT-101 is a Phase 1/2a dose escalation and expansion study to investigate the safety, tolerability, PK, and preliminary efficacy of oral + intratumoral (IT) KAT in subjects with HCC.

Description:

Phase 1 will identify the optimal dose for oral alone, IT alone and the recommended Phase 2 dose (RP2D) dose for oral + IT together. Once the RP2D is identified, additional subjects will be enrolled into Phase 2a (dose-expansion) to further investigate the efficacy and safety of oral + IT KAT at the RP2D.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 148
• Est. completion date: November 2025
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed HCC not amenable to surgical resection or curative-intent locoregional ablative treatments and who are not eligible for liver transplantation.

• Systemic treatment-naive for unresectable locally advanced or metastatic HCC. In addition, have progressed on, refused or were intolerant to sorafenib, lenvatinib, or atezolizumab in combination with bevacizumab. A maximum of 2 prior lines of systemic therapy (including chemotherapy or targeted therapy, not including locoregional therapy) will be allowed.

• At least one measurable lesion based on RECIST 1.1

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Adequate organ function

Exclusion Criteria:

• Prior to the first administration of the study treatment:

1. Major surgery within 28 days

2. Radiotherapy within 14 days including palliative radiation

3. Use of steroids (except for topical agents) within 14 days

4. Chemotherapy within 3 weeks (6 weeks for nitrosourea compounds)

5. Prior treatment with biologic agents, including hormone therapy, within the last 3 weeks, or at least 5 half-lives, whichever is shorter

6. Tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver

7. Treatment with another investigational product within 4 weeks prior to screening or for which 5 half-lives have not elapsed, whichever is longer

8. Uncontrolled central nervous system (CNS) metastasis

• Any clinically significant abnormal intestinal findings that may interfere with the investigational product

• Severe cardiac disorders or subjects with comorbidities of other serious internal disorders on investigator's judgment

• QTcF > 450 msec or congenital long QT syndrome

• Suspected serious infectious diseases, intestinal paralysis, bowel obstruction, interstitial pneumonia, or pulmonary fibrosis

• Serious underlying medical or psychiatric condition, dementia or altered mental status that would impair the ability to understand informed consent, contraindicate participation in the study or confound the results of the study

• Known human immunodeficiency virus (HIV) infection or chronic or active hepatitis B virus (HBV) hepatitis C virus (HCV). Subjects with HCV who have a documented cure (undetectable HCV ribonucleic acid (RNA) 24 weeks after the end of treatment) may be enrolled.

• Severe physical or mental trauma that results from injury or a wound(s).

• Any condition or non-removable device contraindicated for MRI examination

• Pregnant women or nursing mothers.

• Women of childbearing potential (WOCBP) who are unwilling to use a medically acceptable method of birth control during the study until 185 days after the last dose of study treatment

• Men with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the study until 95 days after the last dose of study treatment.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Fibrolamellar Carcinoma
• Hepatocellular Carcinoma

Intervention

Drug:
• KAT-101
oral dosage form
• KAT-201
IT dosage form

Locations

Country	Name	City	State
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
NewG Lab Pharma

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the Recommended Phase 2 Dose (RP2D) for oral + IT administration	RP2D is defined as the dose at which dose escalation (oral + IT) ceases	24 months
Secondary	To evaluate the safety and tolerability of KAT (oral, IT, and oral + IT) in subjects with HCC	Measured as the number of AEs per CTCAE and changes in laboratory values compared to baseline.	54 months
Secondary	To evaluate the preliminary anti-tumor activity of KAT for oral + IT administration	Overall response rate (ORR) is defined as the proportion of subjects with a best overall response (BOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and/or mRECIST; disease control rate (DCR), defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD); duration of response (DOR), defined as the length of time from the time of response (CR or PR) to the time of PD or death; progression-free survival (PFS), defined as the time from the date of treatment initiation to PD or death; overall survival (OS), defined as the length of time from the date of treatment initiation to death from any cause.	54 months
Secondary	To assess maximum concentration (Cmax) of KAT (oral and oral + IT)	Blood samples will be drawn to determine Cmax of KAT	54 months
Secondary	To assess median time to the maximum drug concentration (Tmax) of KAT (oral and oral + IT)	Blood samples will be drawn to determine Tmax of KAT	54 months
Secondary	To assess half lives (T1/2) of KAT (oral and oral + IT)	Blood samples will be drawn to determine T1/2 of KAT	54 months
Secondary	To assess area under the curve (AUC) of KAT (oral and oral + IT)	Blood samples will be drawn to determine AUC of KAT	54 months