Clinical trial NCT05603572: KAT-101 in Subjects With Hepatocellular Carcinoma (HCC)
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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Hepatocellular Carcinoma
Fibrolamellar Carcinoma
Lead sponsor: Primocure Pharma
Sponsor class: INDUSTRY
First posted: 2022-11-02
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. Oral administration (KAT-101)
2. IT administration (KAT-201)
3. Oral administration (KAT-101) + IT administration (KAT-201)
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To determine the Recommended Phase 2 Dose (RP2D) for oral + IT administration
timeFrame: 24 months
Secondary outcomes:
measure: To evaluate the safety and tolerability of KAT (oral, IT, and oral + IT) in subjects with HCC
timeFrame: 54 months
measure: To evaluate the preliminary anti-tumor activity of KAT for oral + IT administration
timeFrame: 54 months
measure: To assess maximum concentration (Cmax) of KAT (oral and oral + IT)
timeFrame: 54 months
measure: To assess median time to the maximum drug concentration (Tmax) of KAT (oral and oral + IT)
timeFrame: 54 months
measure: To assess half lives (T1/2) of KAT (oral and oral + IT)
timeFrame: 54 months
measure: To assess area under the curve (AUC) of KAT (oral and oral + IT)
timeFrame: 54 months
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
References: