RZ-001 Earns FDA Fast Track Designation in HCC

RZ-001 has received FDA fast track designation for the treatment of patients with hepatocellular carcinoma.

The FDA has granted fast track designation to the RNA substitution enzyme–based cancer gene therapy RZ-001 for the treatment of patients with hepatocellular carcinoma (HCC), according to an announcement from Rznomics Inc.1

This regulatory decision marks the second such designation for RZ-001, following its receipt of FDA fast track status in November 2023 for patients with glioblastoma (GBM). RZ-001 also received investigational new drug approval in GBM from both the FDA and South Korea’s Ministry of Food and Drug Safety and is approved for compassionate use under the FDA’s expanded access program in this disease setting.

"We believe that this designation recognizes the potential of RZ-001 as an innovative cancer therapy,” Seong-Wook Lee, PhD, chief executive officer and founder of Rznomics, stated in a news release.1 “We are committed to expediting its clinical development to provide effective treatment options for patients suffering from hard-to-treat cancers."

Developed using Rznomics's proprietary trans-splicing ribozyme RNA editing platform, RZ-001 targets and cleaves human telomerase reverse transcriptase (hTERT) mRNA to selectively suppress hTERT expression in cancer cells while inducing cytotoxic effects through trans-ligation of an HSVtk-encoding sequence into reprogrammed hTERT mRNA.2 Additionally, RZ-001 promotes immune cell infiltration into tumors, reduces VEGF expression, and modulates the tumor microenvironment to enhance responsiveness to immunotherapy.

Preclinical studies have demonstrated therapeutic activity with RZ-001 and dose-dependent improvements in anticancer activity, particularly when administered in combination with atezolizumab (Tecentriq).1

Ongoing Evaluations of RZ-001 in HCC and GBM

RZ-001 is currently being evaluated in combination with the antiviral agent valganciclovir or valganciclovir plus atezolizumab and bevacizumab (Avastin), respectively, for adult patients with hTERT-positive HCC in 2 multicenter, open-label, randomized phase 1b/2a trials (NCT05595473; NCT06695026).3,4

Eligible patients in both trials must be 18 years or older, have Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC, an ECOG performance status of 0 or 1, a Child-Pugh score of A to B7, and a life expectancy of at least 3 months. Exclusion criteria across both trials include moderate or severe ascites, non-HCC carcinomas, hepatic encephalopathy, or HIV positivity.

The first phase 1/2 study consists of 2 parts: a dose-escalation phase in which patients receive an intratumoral injection of RZ-001 at 1 of 4 dose levels alongside valganciclovir, and a dose-expansion phase in which a fixed dose of RZ-001, determined in the escalation phase, is administered.3

The study’s primary end points include dose-limiting toxicities (DLTs) in the dose-escalation phase and adverse effects (AEs) across both phases. Secondary end points include overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

In the second phase 1/2 study, a total of 15 patients will receive an intratumoral injection of RZ-001 at 1 of 3 dose levels in combination with valganciclovir, atezolizumab, and bevacizumab.4 Following a review of the data from enrolled patients, the incidence of DLTS will inform dose escalation to the next level.

The study’s primary end points include AEs, assessment of tumor responses in target lesions, and ORR per RECIST 1.1 criteria and HCC mRECIST. Secondary end points include assessment of tumor responses in non-target lesions, PFS, OS, and DOR.

The agent is also being evaluated in an ongoing phase 1/2a trial (NCT06102525) alongside valganciclovir for patients with hTERT-positive GBM.1

References

  1. Rznomics Inc. liver cancer drug candidate secures fast track designation. News Release. Rznomics. February 17, 2025. Accessed February 21, 2025. https://rznomics.com/bbs/?so_table=promote_en&mode=VIEW&num=110&category=&findType=&findWord=&sort1=&sort2=&page=1&PHPSESSID=9a95f14b982a4fa40f28d4d71ae21ee8
  2. RZNOMICS Inc. announces clinical trial collaboration and supply agreement to evaluate RZ-001 in combination with anti-PDL1 in liver cancer patients. News release. Rznomics Inc. November 10, 2023. Accessed February 21, 2025. https://rznomics.com/bbs/?so_table=promote_en&mode=VIEW&num=88&category=&findType=&findWord=&sort1=&sort2=&page=3
  3. A study to evaluate the safety, tolerability and efficacy of RZ-001 with valganciclovir (VGCV) in subjects with hepatocellular carcinoma. ClinicalTrials.gov. Updated November 4, 2024. Accessed February 21, 2025. https://www.clinicaltrials.gov/study/NCT05595473
  4. A study to evaluate the safety, tolerability and efficacy of RZ-001 with valganciclovir (VGCV) and atezolizumab/​bevacizumab in subjects with hepatocellular carcinoma. ClinicalTrials.gov. Updated January 8, 2025. Accessed February 21, 2025. https://clinicaltrials.gov/study/NCT06695026