FDA Withdraws Krazati/Erbitux Approval in KRAS G12C-Mutated Colorectal Cancer

The FDA has withdrawn its accelerated approval of Krazati (adagrasib) combined with Erbitux (cetuximab) for adults with KRAS G12C-mutated colorectal cancer that is locally advanced or has spread to other parts of the body. The withdrawal, which took effect Sept. 1, 2026, comes after a follow-up study failed to show that the combination helped people live longer than chemotherapy.

The FDA first granted accelerated approval to this combination in June 2024 for people with KRAS G12C-mutated colorectal cancer who had already received chemotherapy containing fluoropyrimidine, oxaliplatin and irinotecan. That approval came with a requirement: a follow-up trial had to confirm that the drug combination truly helped people, not just that tumors shrank. The withdrawal is listed on the FDA's list of withdrawn cancer accelerated approvals and is also noted in Krazati's prescribing information.

Why did the FDA withdraw this approval?

The decision follows final results from the phase 3 KRYSTAL-10 trial, the study designed to confirm the drug combination's benefit. That trial found no meaningful difference between Krazati plus Erbitux and chemotherapy in how long people lived without their cancer getting worse, or in how long people lived overall.

Researchers shared these results at the European Society of Medical Oncology Gastrointestinal Cancers Congress 2026.

What did the KRYSTAL-10 trial find?

The trial enrolled 461 people with KRAS G12C-mutated colorectal cancer that had spread and had worsened after a first round of chemotherapy. Half received Krazati plus Erbitux, and half received chemotherapy chosen by their doctor.

People who received the Krazati combination lived a median of 7.5 months without their cancer worsening, compared with 8.1 months for those on chemotherapy. That difference was not considered statistically meaningful.

People on the drug combination lived a median of 21.6 months overall, compared with 21.7 months for those on chemotherapy. Again, this difference did not meet the bar for statistical significance.

Tumors did shrink more often with the drug combination: 47% of people responded to Krazati plus Erbitux, compared with 16% of people who received chemotherapy. However, that higher response rate did not translate into people living longer or going longer without their cancer worsening, which is why the confirmatory trial did not succeed.

How was the KRYSTAL-10 trial designed?

KRYSTAL-10 was an open-label, randomized trial that compared Krazati, taken twice daily, plus Erbitux against chemotherapy regimens known as FOLFIRI or mFOLFOX6. It enrolled people with KRAS G12C-mutated colorectal cancer that had spread and progressed after a first-line chemotherapy regimen containing oxaliplatin or irinotecan. People who had already received an anti-EGFR antibody or a KRAS G12C-targeted therapy were not eligible.

The trial measured two main outcomes: how long people lived without their cancer worsening, and how long people lived overall.

What side effects did people experience?

Serious side effects related to treatment occurred in 9% of people who received Krazati plus Erbitux, compared with 12% of those who received chemotherapy. Side effects led people to stop treatment in 3% of the Krazati group and 2% of the chemotherapy group.

Higher-grade side effects related to treatment were reported in 46% of people who received the drug combination, compared with 55% of those who received chemotherapy.

What does this mean for people with colorectal cancer?

This withdrawal applies only to the colorectal cancer indication for Krazati plus Erbitux. Krazati's approval for KRAS G12C-mutated non-small cell lung cancer, granted in December 2022, is not affected.

For people with KRAS G12C-mutated colorectal cancer, Krazati plus Erbitux is no longer an FDA-approved treatment option. People currently receiving this combination should talk with their care team about next steps and other treatment options.

References

1. Withdrawn | Cancer Accelerated Approvals - Krazati (Adagrasib). US Food and Drug Administration. Updated September 2, 2026. Accessed September 8, 2026.
2. Krazati (adagrasib) tablets, for oral use. Prescribing information. Bristol Myers Squibb. 2022. Accessed September 8, 2026.
3. FDA grants accelerated approval to adagrasib with cetuximab for KRAS G12C-mutated colorectal cancer. News release. FDA. June 21, 2024. Accessed September 8, 2026.
4. Tabernero J, Kopetz S, Lee J, et al. Second-line adagrasib plus cetuximab vs chemotherapy in patients with KRASG12C-mutated metastatic colorectal cancer: Results from the KRYSTAL-10 trial. Ann Oncology. 2026;37(suppl_1):S1-S76. doi:10.1016/annonc/annonc2111
5. Phase 3 study of MRTX849 with Cetuximab vs chemotherapy in patients with advanced colorectal cancer with KRAS G12C mutation (KRYSTAL-10). ClinicalTrials.gov. Updated July 23, 2026. Accessed September 8, 2026.
6. FDA grants accelerated approval to adagrasib KRAS G12C-mutated NSCLC. News release. ASCO. December 13, 2022. Accessed September 8, 2026.

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