With their Respective Immunotherapy Drugs, Arcus, AstraZeneca Combine to Combat Lung Cancer
By Daniel Ojeda, Ph.D.
On October 29th, Arcus Biosciences announced a collaboration with AstraZeneca to conduct Phase 3 clinical trial to determine the efficacy of Domvanalimab (AB154) treatment in combination with Imfinzi (Durvalumab) in patients with inoperable non-small-cell lung cancer (NSCLC). Each company will maintain the rights for their respective molecules as well as any future profits.
In the United States, lung cancer the second most common type of cancer in men and women, with over 200,000 new cases and over 100,000 deaths estimated in 2020. Out of all lung cancers, approximately 84% are NSCLC. Patients with locally advanced (Stage III), unresectable NSCLC have a 5-year survival rate of approximately 15%-30%.
Two is Better Than One
Imfinzi, developed by AstraZeneca, is a monoclonal antibody that binds to the PD-L1 checkpoint protein expressed by cancer cells to overcome the body’s immune system. In September, AstraZeneca presented results of the PACIFIC Phase 3 clinical trials for Imfinzi in patients with NSCLC. Patients treated with Imfinzi had a higher 4-year survival rate than patients in placebo (49.6% vs. 36.3%).
Domvanalimab, developed by Arcus Biosciences, is a monoclonal antibody targeting TIGIT, another checkpoint protein. Arcus is currently testing Domvanalimab combined with their own PD-1 inhibitor, Zimberelimab, in Phase 2 clinical trial, ARC-7.
With the collaboration, Arcus has gained the unique opportunity to jump to the front of the TIGIT race. As expressed by Dr. Bill Grossman, Chief Medical Officer of Arcus, “This collaboration provides a unique opportunity for Domvanalimab, our novel anti-TIGIT antibody, to be combined with the definitive standard of care in the curative-intent setting of unresectable Stage III NSCLC and to leverage AstraZeneca’s experience, deep knowledge, and leadership within this indication,” He added, “With the aggressive development of our anti-TIGIT antibody in this additional setting, we are well-positioned to be a leader in both the anti-TIGIT field and more broadly in the creation, development, and commercialization of the next generation of innovative immuno-oncology combination therapies.”
It is important to point out that both companies will maintain the right to their own molecules, and they will split the cost of the clinical trials. Additionally, Arcus could end up paying for only 25% of the cost of the clinical trial. Back in July 2020, Gilead and Arcus signed an option and co-development and co-commercialization agreement. If Gilead decides to exercise its option for Domvanalimab, it could split the cost of half of the clinical trial with Arcus.
Due to the promising nature of checkpoint inhibitors, several companies are trying monotherapy and combination therapies using TIGIT inhibitors. Currently, Genentech is conducting Phase 3 clinical trials for their TIGIT inhibitor, Tiragolumab. On Phase 2 clinical trials, we have Merck, with MK‐7684, which is expected to finish by 2032. Next, Bristol-Myers Squibb and their inhibitor BMS-986207, as well as iTeos Therapeutics, are not far behind, currently in Phase 1/2 clinical trials. Finally, in Phase 1 clinical trials, we have Compugen, which, apart from targeting TIGIT, targets PVRIG protein as part of their therapeutic approach.
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