The U.S. Food and Drug Administration (FDA) has accepted supplemental Biologics License Applications (sBLAs) and granted Priority Review to atezolizumab (Tecentriq) and atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza), each in combination with chemotherapy, for the adjuvant treatment of stage III deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) colon cancer. The applications are supported by results from the Phase III Alliance ATOMIC study, which demonstrated a significant disease-free survival (DFS) benefit with atezolizumab plus mFOLFOX6 following surgical resection. The FDA is expected to issue a decision by October 9, 2026.

Clinical Takeaway

Adding atezolizumab to mFOLFOX6 chemotherapy as adjuvant therapy in resected stage III dMMR colon cancer reduced the risk of disease recurrence or death by 50% versus chemotherapy alone. At a median follow-up of 40.9 months, the 3-year DFS rate was 86.3% with atezolizumab plus mFOLFOX6 versus 76.2% with mFOLFOX6 alone. These findings, published in The New England Journal of Medicine and now supporting FDA Priority Review, position atezolizumab plus chemotherapy as a potential new adjuvant treatment option in this biomarker-selected population.

Drug Profile & Mechanism

  • Drug names: Atezolizumab (Tecentriq; Genentech) and atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza; Genentech)
  • Drug class: Anti-PD-L1 monoclonal antibody (immune checkpoint inhibitor)
  • Mechanism: Atezolizumab binds to PD-L1, blocking its interactions with PD-1 and B7.1 receptors and thereby reactivating T cells and enhancing antitumor immune activity
  • Formulations: Available as intravenous (IV) atezolizumab and subcutaneous (SC) atezolizumab and hyaluronidase-tqjs — the first PD-(L)1 cancer immunotherapy available in both delivery modes

Target Population

  • Indication under review: Atezolizumab or atezolizumab and hyaluronidase-tqjs, each in combination with chemotherapy, for the adjuvant treatment of stage III dMMR/MSI-H colon cancer following surgical resection
  • Biomarker requirement: Tumors must demonstrate deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) status. In ATOMIC, dMMR was determined by immunohistochemistry (IHC), including tests such as the VENTANA® MMR RxDx Panel
  • Epidemiologic context:
    • Colon cancer affects over 1 million people globally each year
    • Approximately 30% of stage III patients relapse within five years despite surgery and chemotherapy
    • Approximately 15% of colon cancers are dMMR/MSI-H, a tumor phenotype characterized by higher mutation rates and the potential for increased responsiveness to immunotherapy

Study Design

  • Trial name: ATOMIC (A021502; NCT02912559)
  • Design: Phase III, randomized, open-label, multicenter study
  • Sponsor: National Cancer Institute (NCI); conducted by the Alliance for Clinical Trials in Oncology in partnership with Genentech and the Arbeitsgemeinschaft Internistische Onkologie (AIO) group in Germany
  • Enrollment: 712 patients with resected stage III dMMR colon cancer
  • Randomization: 1:1
    • Experimental arm: mFOLFOX6 + atezolizumab for 12 cycles (6 months), followed by atezolizumab monotherapy for 13 additional cycles (6 months)
    • Control arm: mFOLFOX6 alone for 12 cycles (6 months)
  • dMMR determination: By immunohistochemistry (IHC), with local testing and retrospective central confirmation

Endpoints

  • Primary endpoint: Disease-free survival (DFS)
  • Secondary endpoints: Overall survival (OS) and safety

Efficacy Outcomes

  • Median follow-up: 40.9 months
  • Risk reduction: Adding atezolizumab to mFOLFOX6 reduced the risk of disease recurrence or death by 50% compared with mFOLFOX6 alone (HR, 0.50; 95% CI, 0.35–0.73; P<.001)
  • 3-year DFS rate:
    • mFOLFOX6 + atezolizumab: 86.3%
    • mFOLFOX6 alone: 76.2%
  • These results represent an approximately 10.1-percentage-point absolute improvement in 3-year DFS in patients with stage III dMMR colon cancer
  • Overall survival: OS data remain immature, and no significant OS difference has been demonstrated at this time.

Safety

  • The safety profile of atezolizumab plus mFOLFOX6 was consistent with the known safety profiles of the individual agents; however, grade 3 or 4 adverse events occurred more frequently with atezolizumab plus mFOLFOX6 than with mFOLFOX6 alone (84.1% vs. 71.9%)
  • The most common grade 3 or 4 adverse events included decreased neutrophil count, peripheral sensory neuropathy, and fatigue

Key Clinical Implications

✔ Biomarker-driven selection is essential: The DFS benefit of adjuvant atezolizumab was demonstrated specifically in stage III dMMR colon cancer; routine MMR/MSI testing in all newly diagnosed colon cancers is critical for identifying potentially eligible patients.

✔ A potential paradigm shift in adjuvant colon cancer care: If approved, atezolizumab plus chemotherapy would provide a new immunotherapy-based adjuvant treatment option for stage III dMMR/MSI-H colon cancer, addressing an area of high unmet need where approximately 1 in 3 patients with stage III disease relapse within five years.

✔ Durable benefit with finite immunotherapy exposure: The ATOMIC regimen provides approximately 12 months of total atezolizumab exposure—6 months with mFOLFOX6 followed by 6 months of atezolizumab monotherapy—offering a time-limited treatment strategy with a clinically meaningful 3-year DFS improvement.

✔ Subcutaneous formulation included in the filing: The FDA filing includes both IV Tecentriq and SC Tecentriq Hybreza, potentially providing an additional administration option if the indication is approved.

✔ FDA action expected by October 9, 2026: The FDA is expected to issue a decision by October 9, 2026. Until then, this use of atezolizumab remains under FDA review and is not yet an FDA-approved indication.

Bottom Line

The Phase III ATOMIC trial demonstrated that adding adjuvant atezolizumab to mFOLFOX6 reduced the risk of disease recurrence or death by 50% and improved the 3-year DFS rate from 76.2% to 86.3% in patients with resected stage III dMMR colon cancer. Based on these findings, the FDA has granted Priority Review to IV Tecentriq and SC Tecentriq Hybreza, each in combination with chemotherapy, with a decision expected by October 9, 2026. If approved, this approach would provide a new biomarker-directed adjuvant treatment option for stage III dMMR/MSI-H colon cancer. Oncology clinicians should ensure routine MMR/MSI testing is in place to identify potentially eligible patients.

Sources: