A Study to Evaluate the Safety, Tolerability and Efficacy of RZ-001 With Valganciclovir (VGCV) in Subjects With Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
This is first in human study to evaluate the safety, tolerability, immunogenicity, and preliminary clinical activity of RZ-001 when given to subjects with human telomerase reverse transcriptase (hTERT)-positive HCC.

Detailed Description
-----------------
The study will be conducted in 2 parts. Part 1 is a dose escalation study which aims to explore the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) after the single escalating dose of the intratumoral (IT) injection given through 4 different cohorts. Part 2 will consist of dose expansion, exploring clinical activity for the optimal fixed dose based on the results of Part 1.

Official Title
-----------------
A Phase 1/2a, Open-label, Multicenter, Dose Escalation and Dose Expansion Study Evaluating the Safety, Tolerability and Efficacy of RZ-001 in Combination With Valganciclovir in Subjects With Hepatocellular Carcinoma

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Drug: RZ-001 Dose 1
* Drug: RZ-001 Dose 2
* Drug: RZ-001 Dose 3
* Drug: RZ-001 Dose 4


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult males and females Hepatocellular carcinoma diagnosis (BCLC stage B or C) hTERT positive expression confirmed during the screening period ECOG score of 0 or 1 Child-Pugh score of A to B7 Life expectancy >= 3 months Exclusion Criteria: Moderate or severe ascites History of hepatic encephalopathy Carcinomas other than HCC Current or history of HIV positive Not suitable for inclusion judged by the investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br> | Drug: RZ-001 Dose 1<br>* RZ-001 Dose 1 and VGCV<br>|
| Experimental: Cohort 2<br> | Drug: RZ-001 Dose 2<br>* RZ-001 Dose 2 and VGCV<br>|
| Experimental: Cohort 3<br> | Drug: RZ-001 Dose 3<br>* RZ-001 Dose 3 and VGCV<br>|
| Experimental: Cohort 4<br> | Drug: RZ-001 Dose 4<br>* RZ-001 Dose 4 and VGCV<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Dose limiting toxicities (DLT) in Part 1 as graded by NCI-CTCAE |  | Day 1 to Day 28 | 
| To determine safety and efficacy of RZ-001 by changes in overall response rate (ORR) for participants in part 2 as graded by RECIST v1.1 and mRECIST |  | Day 1 to Day 15 | 
| To determine safety and efficacy of RZ-001 by changes in duration of response (DOR) in part 2 as graded by RECIST v1.1 and mRECIST |  | Day 1 to Day 15 | 
| To determine safety and efficacy of RZ-001 by changes in Progression free survial (PFS) of participants in part 2 as graded by RECIST v1.1 and mRECIST |  | Day 1 to Day 15 | 
| To determine safety and efficacy of RZ-001 by changes in overall survival (OS) of participants in part 2 as graded by RECIST v1.1 and mRECIST |  | Day 1 to Day 15 | 
| Number of participants with adverse events (AEs) in part 1 and 2 as graded by NCI-CTCAE |  | Day 1 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine safety and efficacy of RZ-001 by changes in overall response rate (ORR) of the partipants in Part 1 as graded by RECIST v1.1 and mRECIST |  | Day 1 to Day 15 | 
| To determine safety and efficacy of RZ-001 by changes in duration of response (DOR) of the partipants in Part 1 as graded by RECIST v1.1 and mRECIST |  | Day 1 to Day 15 | 
| To determine safety and efficacy of RZ-001 by changes in Progression free survial (PFS) of the partipants in Part 1 as graded by RECIST v1.1 and mRECIST |  | Day 1 to Day 15 | 
| To determine safety and efficacy of RZ-001 by changes in overall survival (OS) of the partipants in Part 1 as graded by RECIST v1.1 and mRECIST |  | Day 1 to Day 15 |