Is Arcus Biosciences (RCUS) the dark horse of cancer immunotherapy after 26.7-month survival data?

Arcus Biosciences Inc. (NYSE: RCUS) saw its shares climb by nearly 16% on October 13, 2025, closing at USD 16.93 after the company released new clinical data from its Phase 2 EDGE-Gastric study. The surge followed the announcement that a combination regimen featuring domvanalimab and zimberelimab, along with standard chemotherapy, resulted in a median overall survival of 26.7 months in patients with advanced or unresectable gastroesophageal adenocarcinoma.

The results, from Arm A1 of the ongoing EDGE-Gastric trial, are set to be presented at the European Society for Medical Oncology (ESMO) 2025 Congress on October 18, adding visibility to Arcus Biosciences’ TIGIT checkpoint inhibitor strategy. Institutional investors and traders responded swiftly to the data, which are now being viewed as a significant milestone in the development of differentiated combination therapies in immuno-oncology.

What is the significance of 26.7-month overall survival in first-line gastric cancer therapy?

The 26.7-month median overall survival reported in the Phase 2 EDGE-Gastric Arm A1 far exceeds survival benchmarks typically associated with standard-of-care checkpoint inhibitor combinations. Historically, combinations such as nivolumab plus chemotherapy have yielded median survival times ranging from 12 to 15 months in similar patient populations.

This new data from Arcus Biosciences therefore represents a near-doubling of survival expectations, particularly in a disease where prognosis remains poor despite frontline checkpoint inhibition. Survival at 24 months was reported at 50.2% overall, with patients in the PD-L1-high subgroup seeing a 56.3% two-year survival rate. Progression-free survival (PFS) reached a median of 12.9 months in the overall cohort and extended to 14.5 months in the PD-L1-high group.

Dr. Sun Young Rha, professor of medical oncology at Yonsei University in Korea, noted in Arcus’ release that these results significantly exceed thresholds for clinical relevance and demonstrate the promise of anti-TIGIT based regimens in treating upper gastrointestinal cancers.

How did the domvanalimab–zimberelimab–chemotherapy combo perform across subgroups?

The EDGE-Gastric Arm A1 trial enrolled 41 patients with previously untreated, advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. All patients received domvanalimab (1,600 mg IV every 4 weeks) and zimberelimab (480 mg IV every 4 weeks) alongside a bi-weekly FOLFOX regimen (oxaliplatin, leucovorin, and fluorouracil).

Efficacy was observed across all PD-L1 subgroups, with even stronger outcomes in PD-L1-positive and PD-L1-high populations. The confirmed objective response rate (ORR) was 59% in the intent-to-treat cohort, 62% in PD-L1-positive patients, and an impressive 69% in PD-L1-high cases. One patient lacked tissue for central testing but was classified as PD-L1-low based on local testing.

At the time of the data cutoff in March 2025, median study follow-up was 26.4 months, with a median on-treatment duration of 49 weeks. Importantly, no unexpected safety signals emerged. Immune-mediated adverse events occurred in 22% of patients, and infusion-related reactions were reported in just 7%, demonstrating a tolerable safety profile similar to standard PD-1 checkpoint therapy.

What differentiates domvanalimab from other TIGIT antibodies in clinical development?

Domvanalimab is the first and most clinically advanced Fc-silent anti-TIGIT antibody. Its Fc-silent design prevents the depletion of peripheral regulatory T cells, potentially reducing immune-related toxicity while still enabling checkpoint inhibition. TIGIT is a critical inhibitory receptor on immune cells, and blocking it is believed to unlock more robust T-cell activity against tumors.

Unlike Fc-competent TIGIT antibodies that may engage immune effector functions (such as antibody-dependent cell-mediated cytotoxicity), domvanalimab’s design allows it to neutralize TIGIT without engaging destructive immune mechanisms. This allows the immune system to remain active in anti-tumor responses while minimizing systemic toxicity.

Arcus is also testing domvanalimab in combination with zimberelimab, its proprietary anti-PD-1 antibody. Together, these agents form a dual-checkpoint blockade strategy targeting complementary immune escape mechanisms. Zimberelimab itself has demonstrated high affinity and selectivity for PD-1 and has been approved in China for certain cancers through a licensing arrangement with Guangzhou Gloria Biosciences. However, it remains investigational outside China.

What is the role of the Phase 3 STAR-221 study in Arcus’ commercial ambitions?

The positive EDGE-Gastric data sets the stage for Arcus Biosciences’ Phase 3 STAR-221 study, which is already enrolling approximately 1,050 patients with the same upper gastrointestinal cancers. The randomized trial includes two domvanalimab–zimberelimab arms versus standard nivolumab-based therapy across PD-L1-high, PD-L1-positive, and intent-to-treat cohorts.

The STAR-221 study is structured to assess overall survival as its primary endpoint and includes key secondary endpoints such as progression-free survival, objective response rate, and duration of response. Patients were randomized to receive either domvanalimab–zimberelimab plus FOLFOX or CAPOX (capecitabine + oxaliplatin) or standard nivolumab combinations using the same chemotherapy backbones.

If STAR-221 reproduces the survival advantage seen in EDGE-Gastric, it could provide the foundation for regulatory approval and potential commercialization. Arcus’ development model, in partnership with Gilead Sciences, allows it to maintain global rights while benefitting from clinical trial synergies and capital support.

How are investors reacting to Arcus Biosciences’ immunotherapy momentum?

Investor sentiment turned decisively bullish on October 13 following the clinical update. The stock opened at USD 15.80, compared to the previous close of USD 14.60, and quickly soared to an intraday high of USD 16.97. The sharp movement reflects growing institutional confidence in Arcus’ differentiated pipeline and market readiness to reward clear signs of survival benefit in immunotherapy trials.

Market capitalization now stands at approximately USD 1.8 billion. The rally marks a reversal in sentiment from earlier this year when TIGIT checkpoint inhibitors—particularly Roche’s tiragolumab—faced setbacks in other indications. With Arcus producing both safety and efficacy signals, its Fc-silent approach could be perceived as more viable and scalable.

No formal analyst upgrades were released immediately, but biotech-focused investors are increasingly viewing Arcus Biosciences as a credible TIGIT player with the potential to secure first-in-class or best-in-class status depending on Phase 3 outcomes.

What does this mean for the TIGIT field and potential rivals in immuno-oncology?

The TIGIT checkpoint pathway has long been considered a promising next-generation target after PD-1/PD-L1 inhibition. However, enthusiasm has been tempered by mixed trial results and concerns about whether TIGIT inhibition alone can meaningfully improve patient outcomes.

Arcus’ new data changes that narrative by showing substantial survival benefit, durable progression-free survival, and a favorable safety profile when combining TIGIT and PD-1 inhibition with chemotherapy. This places Arcus in a leadership position among TIGIT developers, particularly as it owns both agents in the combination and has multiple registrational trials ongoing.

Beyond gastric cancer, domvanalimab–zimberelimab is being evaluated in non-small cell lung cancer and potentially other tumor types. Its multi-indication strategy, backed by Gilead’s support and Arcus’ in-house immunology expertise, gives it an edge in building a platform, not just a product.

How does this position Arcus Biosciences for long-term growth and value creation?

Founded in 2015, Arcus Biosciences has been steadily building its oncology platform around biology-first drug discovery. With multiple differentiated investigational candidates now in late-stage development, the company is at an inflection point. In addition to domvanalimab and zimberelimab, its pipeline includes casdatifan (a HIF-2α inhibitor for renal cancer) and quemliclustat (a CD73 inhibitor for pancreatic cancer), all of which target immune and metabolic vulnerabilities in cancer cells.

As immunotherapy increasingly shifts toward combination strategies and biomarker-enriched populations, Arcus is emerging as a serious contender. If the STAR-221 trial confirms current data, Arcus could redefine expectations for TIGIT therapeutics and become a central figure in the next wave of cancer immunotherapy.

What could the 26.7-month survival signal from Arcus Biosciences mean for the future of TIGIT-based cancer immunotherapy?

Arcus Biosciences’ 26.7-month median overall survival result in advanced gastric cancer represents more than just a data point—it could mark a definitive turning point for the company’s TIGIT-based immunotherapy platform and potentially for the broader landscape of immune checkpoint combinations. In a therapeutic area where existing PD-1 plus chemotherapy regimens typically yield survival in the 12–15-month range, this new benchmark—combined with consistent performance across PD-L1 subgroups—positions domvanalimab and zimberelimab as serious contenders for first-line standard of care.

For Arcus Biosciences, this milestone could catalyze a transition from a clinical-stage innovator into a commercially relevant oncology player. With the Phase 3 STAR-221 trial already underway and designed to confirm these findings at scale, the company now finds itself at the center of renewed institutional and regulatory attention. Analysts are likely to recalibrate expectations not only for the TIGIT class but for combination immunotherapy development paths that emphasize Fc-silent engineering and tumor-specific synergy.

If the STAR-221 readout replicates the EDGE-Gastric survival gains, Arcus could unlock multiple strategic options—from potential accelerated approvals to global licensing deals or M&A interest from larger biopharma players seeking differentiated assets. For investors, regulators, and pharmaceutical partners evaluating the next wave of oncology innovation, Arcus Biosciences may no longer be viewed as a speculative small-cap biotech but rather as a foundational player in shaping checkpoint inhibitor evolution and long-term cancer treatment paradigms.