FDA Approves Atezolizumab/Chemo for Stage III dMMR/MSI-H Colon Cancer

The FDA has approved atezolizumab (Tecentriq) in combination with chemotherapy for the adjuvant treatment of patients 2 years and older with stage III mismatch repair deficient (dMMR) colon cancer, and atezolizumab with hyaluronidase-tqjs (Tecentriq Hybreza) in combination with chemotherapy for the adjuvant treatment of patients 12 years and older with stage III dMMR disease who weigh 40 kg or greater, according to a news release from the agency.¹ Chemotherapy consists of a fluoropyrimidine and oxaliplatin.

CancerNetwork^® previously reported that the FDA granted priority review to the supplemental biologics license application in June 2026, with a Prescription Drug User Fee Act date of October 9, 2026.²

The recommended dose of intravenous atezolizumab for adult patients is 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks in combination with chemotherapy for 6 months, followed by single-agent atezolizumab for 6 months or until disease recurrence or unacceptable toxicity. For pediatric patients, it is 10 mg/kg (up to a maximum of 840 mg) every 2 weeks or 15 mg/kg (up to a maximum of 1200 mg) every 3 weeks plus chemotherapy for 6 months, followed by single-agent atezolizumab for 6 months or until disease recurrence or unacceptable toxicity.

The recommended dose of atezolizumab and hyaluronidase-tqjs for adult and pediatric patients 12 years of age who weigh 40 kg or greater is one 15 mL injection every 3 weeks administered subcutaneously in combination with chemotherapy for 6 months, followed by monotherapy of atezolizumab and hyaluronidase-tqjs for 6 months or until disease recurrence or unacceptable toxicity. The 15 mL injection contains 1875 mg of atezolizumab and 30,000 units of hyaluronidase. For pediatric patients under 12 years of age and 12 years or older who weigh less than 40 kg, the recommended dose has not yet been established.

What were the efficacy results from the ATOMIC trial?

Both the priority review designation and approval were supported by data from the phase 3 ATOMIC/Alliance A021502 trial (NCT02912559).^3,4 It was previously announced that the study met its primary end point of disease-free survival (DFS) via a publication in the New England Journal of Medicine. At a median follow-up of 40.9 months (IQR, 26.7-58.6), atezolizumab plus modified FOLFOX6 (mFOLFOX6; fluorouracil, oxaliplatin, leucovorin) reduced the risk of recurrence or death vs mFOLFOX6 alone (HR, 0.50; 95% CI, 0.35-0.73; P <.001). The 3-year DFS rate was 86.3% (95% CI, 81.8%-89.8%) with the combination vs 76.2% (95% CI, 70.9%-80.6%) with chemotherapy alone.

Overall survival (OS) data were early at a median follow-up of 45.8 months (IQR, 32.0-64.7). There were 31 deaths in the atezolizumab arm and 33 in the control arm (HR, 0.90; 95% CI, 0.55-1.47). The 5-year OS rates were 89.7% and 87.9%, respectively. In an exploratory analysis by mFOLFOX6 duration, among patients who received more than 6 cycles, the HR was 0.41 (95% CI, 0.27-0.64) vs 0.97 (95% CI, 0.44-2.11) for those who received 6 or fewer.

“The results of this study represent a pivotal advancement for the treatment of non-metastatic dMMR colon cancer," Frank A. Sinicrope, MD, Alliance study chair and a physician at Mayo Clinic, stated in a news release from the Alliance for Clinical Trials in Oncology, at the time of the initial result reporting.⁵

How was the ATOMIC trial designed?

ATOMIC is a randomized, open-label, multicenter phase 3 trial that enrolled patients 12 years and older with completely resected stage III dMMR colon cancer and an ECOG performance status of 0 to 2.⁴

A total of 712 patients were enrolled into the trial and randomly assigned 1:1 to mFOLFOX6 every 14 days for 12 cycles with or without atezolizumab. Those in the experimental arm continued atezolizumab alone after chemotherapy for 13 additional cycles.

The primary end point was DFS. Secondary end points included OS and safety. Patients with Lynch syndrome were eligible for enrollment.

What was the safety profile of atezolizumab plus mFOLFOX6?

Grade 3 or 4 adverse events (AEs) occurred in 84.1% of the atezolizumab arm and 71.9% of the control arm. The most common grade 3 or 4 toxicities with the combination were decreased neutrophil count (43.6%), peripheral sensory neuropathy (18.5%), diarrhea (12.1%), and fatigue (10.1%). Six patients in the combination arm and 2 in the control arm had grade 5 events. Investigators judged 2 deaths in the combination arm (1 sudden death and 1 sepsis) to be treatment related.

The prescribing information for this treatment includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem-cell transplantation, and embryo-fetal toxicity.

What does the approval mean for patients with dMMR/MSI-H colon cancer?

The approval adds atezolizumab to the adjuvant setting for stage III dMMR/MSI-H colon cancer, where the standard has been surgery followed by chemotherapy such as FOLFOX.⁵ Approximately 30% of patients with stage III disease relapse within 5 years despite this approach, and that dMMR/MSI-H tumors account for roughly 15% of colon cancers.² According to the company, atezolizumab plus chemotherapy is the first immunotherapy-based adjuvant option for this population.

Until now, FDA-approved immunotherapy in dMMR/MSI-H colorectal cancer has been limited to the advanced and metastatic settings. Those agents include pembrolizumab (Keytruda), nivolumab (Opdivo), and, since April 2025, nivolumab plus ipilimumab (Yervoy) for unresectable or metastatic disease.⁶ With this action, atezolizumab becomes a PD-L1 inhibitor option earlier in the disease course, in patients who have undergone resection and are being treated with curative intent.

References

1. FDA approves atezolizumab in combination with chemotherapy for Stage III mismatch repair deficient colon cancer. News release. FDA. October 8, 2026. Accessed October 8, 2026. https://tinyurl.com/5c3w3f7u
2. FDA grants priority review for Roche's Tecentriq for a certain type of stage III colon cancer. News release. Roche. June 10, 2026. Accessed October 8, 2026. https://tinyurl.com/ybye9md4
3. Sinicrope FA, Ou FS, Arnold D, et al. Atezolizumab plus FOLFOX for stage III mismatch repair-deficient colon cancer. N Engl J Med. 2026;394(12):1115-1126. doi:10.1056/NEJMoa2507874
4. Combination chemotherapy with or without atezolizumab in treating patients with stage III colon cancer and deficient DNA mismatch repair. ClinicalTrials.gov. Updated October 1, 2026. Accessed October 8, 2026. https://tinyurl.com/47k2wysc
5. Landmark Alliance ATOMIC trial establishes new standard of care for patients with stage III dMMR colon cancer. News release. Alliance for Clinical Trials in Oncology. March 25, 2026. Accessed October 8, 2026. https://tinyurl.com/3bv9687k
6. FDA approves nivolumab with ipilimumab for unresectable or metastatic MSI-H or dMMR colorectal cancer. News release. FDA. April 8, 2025. Accessed October 8, 2025. https://tinyurl.com/3vj77rfh