Fibrolamellar Carcinoma, Hepatocellular Carcinoma
Conditions
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.
Interventions
DRUGKAT-101
oral dosage form
DRUGKAT-201
IT dosage form
Sponsors
Primocure Pharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
1. Oral administration (KAT-101) 2. IT administration (KAT-201) 3. Oral administration (KAT-101) + IT administration (KAT-201)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the Recommended Phase 2 Dose (RP2D) for oral + IT administration | 24 months | RP2D is defined as the dose at which dose escalation (oral + IT) ceases |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the preliminary anti-tumor activity of KAT for oral + IT administration | 54 months | 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. |
| To assess maximum concentration (Cmax) of KAT (oral and oral + IT) | 54 months | Blood samples will be drawn to determine Cmax of KAT |
| To evaluate the safety and tolerability of KAT (oral, IT, and oral + IT) in subjects with HCC | 54 months | Measured as the number of AEs per CTCAE and changes in laboratory values compared to baseline. |
| To assess half lives (T1/2) of KAT (oral and oral + IT) | 54 months | Blood samples will be drawn to determine T1/2 of KAT |
| To assess area under the curve (AUC) of KAT (oral and oral + IT) | 54 months | Blood samples will be drawn to determine AUC of KAT |
| To assess median time to the maximum drug concentration (Tmax) of KAT (oral and oral + IT) | 54 months | Blood samples will be drawn to determine Tmax of KAT |
Countries
South Korea
Outcome results
None listed