Phase I Clinical Trial NCT05346494 by Imugene Limited VAXINIA study of CF33-hNIS,
an oncolytic virus, as monotherapy or in combination with Pembrolizumab in adults with metastatic or advanced solid tumors (MAST), including NSCLC
Imugene’s CF33, or Vaxinia, is a modified DNA virus of the Poxviridae family developed by Professor Yuman Fong at the City of Hope Comprehensive Cancer Center in Los Angeles. Vaccinia, or pox, viruses have a track record of safe use in millions of humans, as the original variant was the active constituent of the vaccine that eradicated smallpox, and first proved able to kill cancer cells in 1922. CF33 has the potential to act as both a gene therapy delivery vehicle and an oncolytic (cancer killing) agent. It is derived by Imugene as a combination of genomic sequences from multiple vaccinia virus strains, generating a new, safer, and more potent virus. Vaxinia has a short well characterized life cycle and spreads rapidly from cancer cell to cell, but does not integrate into the host’s genome. It is highly cytolytic (disintegrates cancer cells) for a broad range of tumor cell types. When combined with the Human Sodium-Iodide Symporter (hNIS) gene, CF33-hNIS enables imaging to track the virus in vivo and mediate targeted radiotherapy, making it more accurate.
This is a Phase I, open label (patients know what they are taking), dose escalation, multi-center, safety and tolerability study of Vaxinia (CF33-hNIS). There are four cohorts in the trial, and patients are either injected intratumorally as a monotherapy or with pembrolizumab, or injected intravenously as a monotherapy or with pembrolizumab. Patients eligible for treatment include those with any metastatic or advanced solid tumor who have documented radiological progression following at least two prior lines of therapy which may have included treatment with an Immune Checkpoint Inhibitor. There appear to be no exclusions that would prohibit ALK positive NSCLC patients from participating. The trial began in April, 2022 at City of Hope Medical Center in Duarte California, and at NEXT Oncology in Fairfax, Virginia. Contacts can be found here: https://clinicaltrials.gov/ct2/show/NCT05346484?term=imugene&draw=2&rank=1#contacts
Another clinical development: Vaxinia can also be “armed” with anti PD-L1 genes, which disable PD-L1, the cellular signaling pathway that helps cells tell the immune system not to attack them. With these signals removed, the body’s immune system can actively target and attack the cancer cells. Imugene’s treatment CF33-hNIS-PDL1, or CHECKvacc is currently in Phase I trials at City of Hope Medical Center for the Treatment of Metastatic Triple Negative Breast Cancer. https://clinicaltrials.gov/ct2/show/NCT05081492?term=imugene&draw=2&rank=5#contacts
And a preclinical development: Perhaps most interestingly, Vaxinia, or CF33 is being further designed to express CD-19 Antigens on the surface of cancer cells as a target for existing CD-19-targeting Chimeric Antigen Receptor therapies (CAR T immunotherapies) like Kymriah (Novartis), Breyanzi (Bristol Myers Squibb), and Yescarta (Gilead). These drugs have previously been used effectively in B cell malignancies (blood cancers) that express varying levels of CD-19 antigens naturally, but have shown suboptimal efficacy in solid tumors, which represent around 90% of all cancers world-wide. If solid tumor cells, and perhaps ALK positive NSCLC cells, can be induced to express CD-19 antigens on their surfaces, then such otherwise cold tumors can hopefully be made vulnerable to CD-19 targeting CAR T immunotherapies. Imugene calls this technology CF33+CD19 or onCARlytics, and preclinical studies have supported the case for efficacy in mice. https://www.science.org/doi/10.1126/scitranslmed.aaz1863
CF33+CD19 aka onCARlytics, Imugene Limited, in preclinical development.
Imugene is an Australian company based in Sydney, founded in 2002, and publicly listed on the Australian Securities Exchange (ASX) with the symbol ISU. The company raised investments of $95M in July of 2021 shortly after the end of that fiscal year ending in June, when they showed current assets of $36M and a loss for that year of $18.4M. Imugene recently announced a strategic partnership with Celularity, Inc. (NASDAQ:CELU), a global pioneer in developing placental-derived allogeneic therapies. Celularity’s CyCART-19, when combined with Imugene’s onCARlytics, will create a broadly applicable targeted approach to destroying solid tumors by enabling uniform expression of CD19. Another partnership was announced with privately held Eureka Therapeutics. Their anti-CD19 Artemis T-cell therapy will also combine with Imugene’s onCARlytics in the development of tumorspecific targets for T-cell therapies.
Jeffrey M. Sturm, BS, MA, MBA
ALK Positive www.alkpositive.org
Member, Research Acceleration Committee
Member, Clinical Trials Committee