Key points
- Andes-1537 is a well-tolerated drug with a novel mechanism.
- Maximum tolerated dose (MTD) determined to be 600 mg SQ twice weekly.
- Good safety profile with injection site reactions (ISRs) as most common adverse effect (68%, 13/19)
- Stable disease (SD) for 5 patients (29,5%), two of the five showed SD beyond 6 month
In 2015, Andes Biotechnologies in collaboration with UCSF opened its first-in-human trial to test safety and tolerability of Andes-1537 for subcutaneous injection in patients with advanced unresectable solid tumors that are refractory to standard therapy or for which no standard therapy is available (NCT02508441).
Today, the results of this study were presented to the American Society of Clinical Oncology (ASCO), demonstrating a good safety profile and some preliminary signals of efficacy of the drug. The study included 22 patients with heavily pretreated solid tumors, enrolled in 5 cohorts. The dose-limiting toxicities were two injection site reactions, one precluding full cycle 1 dose delivery, and one involving grade 3 skin necrosis due to vascular occlusion and inflammation. No other grade 3/4 toxicities were seen, and the MTD has been determined to be 600 mg SC twice weekly.
In terms of efficacy, 5 patients showed stable disease, and two of them, one with pancreatic cancer and one with cholangiocarcinoma, had SD on scans beyond six months at 200 mg dose level and thus dose expansion is under consideration.
About Andes-1537
Andes-1537 is a short single stranded phosphorothioate deoxyoligonucleotide which binds by base pairing to one of 2 newly discovered non-coding RNAs, named Antisense non-coding mitochondrial RNA (ASncmtRNA). The resulting RNA-DNA hybrid is then hydrolyzed by two cellular RNases: RNase H and DICER resulting in microRNAs. In vitro experiments with cells have shown Andes-1537 affects cancer cells by a) inducing apoptosis by lowering the expression of anti-apoptotic proteins such as survivin b) decreasing proliferative signaling through inhibition of the expression of proteins such as cyclin D1 and cyclin B1, and c) inhibition of tissue invasion/metastatic proteins such as n-cadherin, B-catenin and metastasis inducing factors.
About Andes Biotechnologies (www.andesbio.com)
The aim of Andes Biotechnologies is to carry out research and development of new anticancer therapies based on the inactivation of novel non-coding mitochondrial RNA targets through anti-sense technology. Andes has a portfolio of more than 70 patent in key markets around the world, covering the diagnostic and therapeutic uses of non-coding mitochondrial RNA oligonucleotides which have the potential of selectively eliminating tumor cells without harming normal cells in many Cancer types. The company has a management team with extensive experience in drug development and biotechnology research, which has successfully developed, patented and registered products currently marketed in the U.S. and Europe.
