FDA clears Tecentriq with chemo after surgery for Stage III dMMR colon cancer

The Food and Drug Administration on Oct. 8 cleared Genentech's Tecentriq with fluoropyrimidine and oxaliplatin chemotherapy as adjuvant treatment for Stage III mismatch repair–deficient colon cancer, a setting where the company says no immunotherapy regimen had been approved after surgery.

What the agency cleared

Genentech, a Roche Group member, said the Food and Drug Administration approved Tecentriq (atezolizumab) with a fluoropyrimidine and oxaliplatin for the adjuvant treatment of Stage III deficient DNA mismatch repair (dMMR) colon cancer. The same day, the agency also cleared Tecentriq Hybreza — the subcutaneous atezolizumab-and-hyaluronidase product — with the same chemotherapy backbone for adults and for patients 12 and older who weigh at least 40 kilograms.

The intravenous Tecentriq label covers adults and pediatric patients two years of age and older. Genentech called the decision the twelfth U.S. indication for Tecentriq and said it is the first approved adjuvant immunotherapy regimen for Stage III dMMR colon cancer.

What the Atomic trial showed

Efficacy came from the Phase III Atomic study (also listed as ML39057 and NCT02912559). The Food and Drug Administration said the trial enrolled 711 adults and one pediatric patient with Stage III dMMR colon cancer after complete resection and with no residual nodal or metastatic disease. Patients were randomized one-to-one to atezolizumab plus mFOLFOX6 for 12 cycles followed by atezolizumab alone for six months, or to mFOLFOX6 alone for 12 cycles.

The primary endpoint was investigator-assessed disease-free survival. The hazard ratio was 0.50 (95% confidence interval 0.35 to 0.73; p-value 0.0001), and median disease-free survival was not reached in either arm. Genentech and Roche said adding Tecentriq cut the risk of recurrence or death by 50% versus chemotherapy alone, with 36-month disease-free survival of 86% on Tecentriq plus mFOLFOX6 versus 76% on chemotherapy alone. The companies said safety matched the known Tecentriq and mFOLFOX6 profiles. Results were published in the New England Journal of Medicine.

How the drug is dosed

For adults, the recommended intravenous atezolizumab doses are 840 mg every two weeks, 1,200 mg every three weeks, or 1,680 mg every four weeks with chemotherapy for six months, then atezolizumab alone for six months or until recurrence or unacceptable toxicity. Pediatric intravenous dosing is weight-based with caps at 840 mg or 1,200 mg, depending on the schedule. Hybreza is given as one 15 mL subcutaneous injection every three weeks (1,875 mg atezolizumab plus 30,000 units of hyaluronidase) with chemotherapy for six months, then as monotherapy for six months in eligible patients.

The review ran under Project Orbis with Australia's Therapeutic Goods Administration, Health Canada, Israel's Ministry of Health, and Switzerland's Swissmedic. Those partner reviews were still open in the Food and Drug Administration notice. Genentech said nearly a quarter of colon cancers are diagnosed at Stage III and that almost one in three of those patients see a recurrence within five years — context the approval does not itself change.

List price, U.S. uptake, and any change to Roche's outlook were not in the Oct. 8–9 releases. Whether other regulators finish Project Orbis reviews on the same terms is also still open.