KAT-101 in Subjects With Hepatocellular Carcinoma (HCC)

Primocure Pharma

Status and phase: Suspended; Phase 2; Phase 1

Conditions: Fibrolamellar Carcinoma; Hepatocellular Carcinoma

Treatments: Drug: KAT-101; Drug: KAT-201

Study type: Interventional

Funder types: Industry

Identifiers

NCT05603572

NLP-KAT-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 148 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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148 participants in 3 patient groups

Oral experimental arm

Experimental group

Description:

Oral administration (KAT-101) taken once per day for 4 consecutive days out of 7 (4 days on / 3 days off weekly). Each cycle is 28 days. Treatment will continue for up to 12 cycles until progressive disease (PD), unacceptable toxicity, or any reason for discontinuing its administration, whichever occurs first.

Treatment:

Drug: KAT-101

IT experimental arm

Experimental group

Description:

IT administration (KAT-201) will be injected via percutaneous IT injection with ultrasound and/or computed tomography (CT) guidance once a week (on Day 1 weekly). Each cycle is 28 days. Treatment will continue for up to 2 cycles until PD, unacceptable toxicity, or any reason for discontinuing its administration, whichever occurs first.

Treatment:

Drug: KAT-201

Oral + IT experimental arm

Experimental group

Description:

Once optimal oral and IT dose are determined, oral + IT will be administered as follows: oral administration (KAT-101) will be taken once per day for 4 consecutive days out of 7 (4 days on / 3 days off weekly). Treatment will continue for up to 12 cycles (each cycle 28 days). IT administration (KAT-201) will be injected via percutaneous IT injection with ultrasound and/or CT guidance once a week (on Day 1 weekly). Treatment will continue for up to 2 cycles (each cycle 28 days) until PD, unacceptable toxicity, or any reason for discontinuing its administration, whichever occurs first.

Treatment:

Drug: KAT-201

Drug: KAT-101