How It’s Made: A Potential New Treatment for Kidney Cancer
This is a sponsored post by Arcus Biosciences, written by Richard Markus, M.D., Ph.D., chief medical officer at Arcus Biosciences.
Ever wonder how a medicine was made? What often starts as a sketch on a piece of paper must undergo a rigorous cycle of trial and error until, ultimately, a new medicine is born. That’s the iterative nature of drug discovery – and it begins with identifying which target to go after.
One such target is hypoxia-inducible factor (HIF)-2α.
HIF-2α is a master switch that turns on hundreds of genes in response to low oxygen levels; when oxygen levels return to normal, HIF-2α is turned off. In a majority of people with the most common form of kidney cancer (clear cell renal cell carcinoma), this shut-off mechanism is deficient and HIF-2α remains activated even in the presence of oxygen, which enables the cancer to grow.
Diligent Design
Building a new molecule, that could change the way patients are treated, requires immense attention to detail. The Arcus team meticulously and deliberately added specific atoms to gradually grow and develop the ideal molecular candidate for an investigational HIF-2α inhibitor treatment called casdatifan.
A key goal in the development process was to optimize several properties to address unmet needs in the current treatment landscape. This included exposure, which is the amount of the molecule that gets absorbed into the bloodstream and distributed to various tissues. By optimizing these properties, the Arcus team hoped to target HIF-2α more completely, including in hard-to-reach places, including organs with cancer.
Up to the Test
Once the investigational HIF-2α inhibitor has cleared tests in the lab, it’s ready to advance to the ultimate challenge of drug development – clinical trials. Today, this HIF-2α inhibitor is being investigated in several clinical studies:
PEAK-1, NCT07011719a Phase 3 study evaluating a HIF-2α inhibitor with a tyrosine kinase inhibitor, which blocks several cancer-driving processes.
ARC-20, NCT05536141, a Phase 1 study investigating a HIF-2α inhibitor alone and in combination with an anti-PD-1 or a tyrosine kinase inhibitor
eVOLVE-RCC02, NCT07000149, a Phase 1/3 study investigating a HIF-2α inhibitor with an anti-PD-1/CTLA-4 immunotherapy that simultaneously blocks two checkpoint inhibitors, allowing the body’s own immune system to find and attack cancer cells.
All of these trials currently focus on people who are just starting their first treatment following their diagnosis, or those who have previously been treated with a cancer immunotherapy. By investigating the combination of a HIF-2α inhibitor with different medicines, and in different lines of treatment, the goal is to stop multiple cancer-driving processes simultaneously at different stages of the treatment journey.
What began as a sketch on a piece of paper has gradually risen to a promising potential new approach for people with ccRCC and could change the way people with kidney cancer are treated.
For more information on Arcus’s trials in the United States and globally, visit trials.arcusbio.com.
Casdatifan is an investigational molecule. Arcus has not received approval from any regulatory authority for any use globally, and its safety and efficacy for the treatment of renal cell carcinoma has not been established.