AstraZeneca and Arcus Biosciences Initiate Pivotal Phase 3 Trial of TIGIT/PD-L1 Inhibitor Combination for Unresectable Stage III NSCLC

Today, Arcus Biosciences announced a collaboration with AstraZeneca to initiate a registrational Phase 3 clinical trial evaluating the efficacy of Arcus’s investigational anti-TIGIT antibody domvanalimab (AB154) in combination with the PD-L1 inhibitor Imfinzi (durvalumab) for the treatment of patients with unresectable Stage III non-small cell lung cancer (NSCLC).

Immune checkpoint inhibitors, represented by PD-1/PD-L1 inhibitors, have brought revolutionary changes to cancer treatment; however, many cancer patients still do not respond to them. Therefore, a key direction in immuno-oncology research is the development of combination therapies based on PD-1/PD-L1 inhibitors to expand the efficacy of immunotherapy and broaden the patient population that benefits from it. Among these, TIGIT is a highly scrutinized target. TIGIT stands for T cell immunoreceptor with Ig and ITIM domains. It is an inhibitory receptor expressed on the surface of various types of immune cells. Signaling pathways mediated by TIGIT can suppress the activity of a range of anti-tumor immune cells.

Domvanalimab (AB154), a monoclonal antibody targeting TIGIT developed by Arcus Biosciences, blocks TIGIT activity at the nanomolar level, thereby inhibiting immune suppression and enhancing immune activity. Domvanalimab has demonstrated favorable safety in clinical trials and is currently undergoing evaluation in Phase 2 clinical trials.

▲Mechanism of Action of TIGIT Inhibitors (Image source: Arcus Biosciences official website)

Results from the phase 3 PACIFIC trial, recently presented at the European Society for Medical Oncology (ESMO) Annual Meeting, demonstrated that treatment with Imfinzi following chemoradiotherapy (CRT) significantly improved survival in patients with unresectable stage III non-small cell lung cancer (NSCLC). An estimated 50% of patients survived for 4 years, compared with 36% in the CRT-alone group; the 4-year progression-free survival rate was 35%, versus 20% in the CRT-alone group.

References:

[1] Arcus to Collaborate With AstraZeneca on Registrational Trial for Domvanalimab, Arcus’s Novel Anti-TIGIT Antibody, Plus Imfinzi® in Stage III NSCLC. Retrieved October 29, 2020, from https://investors.arcusbio.com/investors-and-media/press-releases/press-release-details/2020/Arcus-to-Collaborate-With-AstraZeneca-on-Registrational-Trial-for-Domvanalimab-Arcuss-Novel-Anti-TIGIT-Antibody-Plus-Imfinzi-in-Stage-III-NSCLC/default.aspx

▽Follow [WuXi AppTecDe】WeChat Official Account