FDA Withdraws Adagrasib–Cetuximab Indication for KRAS G12C Metastatic CRC: US FDA | September 2026 | Regulatory Update

Introduction:

Adagrasib + cetuximab received accelerated FDA approval for previously treated KRAS G12C-mutated metastatic colorectal cancer (mCRC). Following failure of the confirmatory KRYSTAL-10 Phase III trial to demonstrate improved survival outcomes, the FDA has now formally withdrawn this indication.

Why is this important?

Accelerated approvals require confirmation of clinical benefit.

KRAS G12C remains an important actionable target in mCRC.

The withdrawal creates an immediate change in the US treatment landscape.

Key Findings:

FDA withdrawal became effective 1 September 2026.

In KRYSTAL-10, 461 second-line patients received adagrasib + cetuximab or chemotherapy.

Median PFS was 7.5 vs 8.1 months (HR 0.89).

Median OS was virtually identical: 21.6 vs 21.7 months.

Despite this, objective response was substantially higher with adagrasib + cetuximab: 47% vs 16%.

Thus, improved tumour response did not translate into superior PFS or OS.

KRYSTAL-10 results remain conference-reported; the FDA withdrawal itself is a formal regulatory action.

Regulatory status outside the US should be assessed separately.

Bottom Line:

Adagrasib + cetuximab is no longer FDA-approved for this CRC indication. KRYSTAL-10 highlights that higher response rates alone do not guarantee meaningful survival benefit.