As the 2024 American Society of Clinical Oncology (ASCO) annual meeting approaches, excitement builds over the latest in cancer treatment advancements. From May 31 to June 4, industry leaders will unveil new data on different therapies. At the 2024 ASCO Annual Meeting, Arcus Biosciences will report updated findings from Phase II and I/II trials of innovative immuno-oncology combinations. The closest upcoming catalysts for Arcus are the Phase I/II studies for etrumadenant (A2a/A2b receptor antagonist) and the Phase II studies for domvanalimab (anti-TIGIT mAb), which are set to be presented during ASCO 2024. 

New Avenues in Gastric Cancer Treatment (Edge-Gastric) & Breakthroughs in Colorectal Cancer Research (ARC-9)

1. Abstract Number – 3508

Title: - Arcus Biosciences is gearing up to present the results of the ARC-9 study, which shows that etrumadenant (AB928) is safe and effective in mCRC patients.

Commentary Data from the ARC-9 study evaluating etrumadenant plus zimberelimab-based treatment combination in third-line metastatic colorectal cancer will be presented in an oral presentation at ASCO 

Executive Summary – AB928, a potent dual antagonist targeting the adenosine receptors A2aR and A2bR, is set to take center stage at the ARC-9 presentation. The eagerly anticipated data will unveil randomized progression-free survival (PFS) and overall survival (OS) outcomes for a combination therapy featuring etrumadenant compared against regorafenib, the established standard of care in third-line colorectal cancer.

Main Content –  

AB928, a potent dual antagonist targeting adenosine receptors A2aR and A2bR, will be the focal point of the ARC-9 study at ASCO 2024. This presentation will feature PFS and OS data from Cohort B of the Phase Ib/II ARC-9 study, evaluating etrumadenant in combination with zimberelimab and FOLFOX (with optional bevacizumab) versus regorafenib for third-line or later metastatic colorectal cancer. Notably, this data will encompass patients with and without liver metastases.

While the trial employs regorafenib as the control arm, it is worth noting that Lonsurf (trifluridine/tipiracil) plus bevacizumab has recently emerged as a third-line standard of care following the Sunlight study, demonstrating median PFS of 5.6 months and median OS of 10.8 months. ARC-9 Cohort A, comparing the same etrumadenant regimen with FOLFOX plus bevacizumab in second-line patients, is still ongoing, with results pending due to the prolonged OS observed in the earlier line setting.

This program is particularly promising due to the limited competition in the third-line mCRC landscape. Unlike many competitors, the trial includes patients with liver metastases, offering a unique opportunity given their significant representation in the patient population. Additionally, the data will shed light on the performance of regorafenib, although Lonsurf plus bevacizumab has gained traction as an additional standard of care since the trial's initiation.

Despite its potential in prostate cancer, Arcus Biosciences and Gilead opted not to advance etrumadenant in this indication after reviewing early clinical data in August 2023. However, the companies continue to explore its efficacy in combination therapies across various cancers.

Conclusion: Post At the upcoming oral presentation, Arcus Biosciences will unveil compelling findings from Cohort B of the ARC-9 trial. This Phase Ib/II study focuses on assessing the safety and efficacy of etrumadenant in combination with zimberelimab, alongside FOLFOX and optional bevacizumab, for third-line mCRC. Etrumadenant's promising performance takes center stage at the prestigious ASCO annual meeting.

2. Abstract Number - 433248

Title: The EDGE-Gastric Arm A1 trial's findings on domvanalimab combined with zimberelimab and FOLFOX for first-line advanced gastroesophageal cancer are anticipated to steal the spotlight 

Commentary - The ASCO plenary series will feature an update from the EDGE-Gastric trial. This eagerly anticipated presentation will showcase the latest data on domvanalimab in combination with zimberelimab and chemotherapy for upper gastrointestinal (GI) cancers. Stay tuned for this rapid abstract update session. 

Executive Summary – The EDGE-Gastric presentation will unveil the median PFS data for the Fc-silent anti-TIGIT antibody combined with zimberelimab and chemotherapy in upper gastrointestinal (GI) cancers.

Main Content – 

Domvanalimab, the pioneering Fc-silent investigational monoclonal antibody targeting T-cell immunoreceptor with Ig and ITIM domains (TIGIT), stands poised to revolutionize cancer treatment. With Gilead and Arcus fortifying their collaboration to accelerate its development, domvanalimab holds promise in reshaping therapeutic paradigms.

The upcoming presentation of mature PFS data from Arm A1 of the Phase II EDGE-Gastric study at ASCO underscores the potential of domvanalimab in first-line upper gastrointestinal cancers. Furthermore, ongoing evaluation in first-line NSCLC patients through the Phase III Star-121 trial, alongside the concurrent Phase III Star-221 trial, positions domvanalimab as a promising candidate with a dual primary endpoint strategy.

While Arcus' TIGIT program is anticipated to demonstrate efficacy comparable to Claudin 18.2 programs, its distinct safety profile offers a competitive advantage, particularly in mitigating gastrointestinal toxicities. As both program types address different patient populations, there is ample room for Arcus' innovative approach alongside existing therapies like zolbetuximab, despite recent regulatory challenges. This highlights the dynamic landscape and potential for significant advancements in cancer immunotherapy. In the evolving landscape of cancer therapeutics, domvanalimab epitomizes innovation, promising efficacy, and safety in equal measure, heralding a new era in oncology.

Conclusion: Domvanalimab's accelerated development, bolstered by Gilead and Arcus' collaboration, marks a significant advancement in cancer treatment. The upcoming presentation of mature data from the Phase II EDGE-Gastric study highlights its potential in upper gastrointestinal cancers. Arcus' TIGIT program, with its distinct safety profile, offers a competitive edge in the landscape, complementing existing therapies like zolbetuximab. In this dynamic environment, domvanalimab emerges as a beacon of innovation, poised to reshape oncology with its efficacy and safety profile.