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# FDA Grants Accelerated Approval to Krazati After 42.9% Response Rate in KRAS G12C-Mutated Lung Cancer
- URL: https://www.theamericanquorum.com/taq-historical-2022-12-17-healthcare/
- Published: 2022-12-18T04:59:00.000Z
- Updated: 2022-12-18T04:59:00.000Z
- Description: Adagrasib won accelerated approval for previously treated KRAS G12C-mutated advanced NSCLC after a 112-patient efficacy cohort produced a 42.9% confirmed response rate.
- Author: Kenneth R. Deans Jr.
- Tags: Healthcare, #Import 2026-08-31 20:02

WASHINGTON — The Food and Drug Administration this week granted accelerated approval to adagrasib, sold as Krazati, for adults with KRAS G12C-mutated locally advanced or metastatic non-small-cell lung cancer who have received at least one prior systemic therapy. The FDA’s [trial snapshot](https://www.fda.gov/drugs/drug-trials-snapshots/drug-trials-snapshots-krazati?ref=theamericanquorum.com) says efficacy was evaluated in 112 patients and safety in 366 patients from the KRYSTAL-1 program.

The approval adds a second targeted drug against KRAS G12C, a mutation long viewed as difficult to drug because of the structure and signaling behavior of the KRAS protein. In the registrational cohort, 48 of 112 patients with measurable disease had a confirmed objective response, a rate of 42.9%, and median duration of response was 8.5 months. Those results were published earlier this year in the [New England Journal of Medicine](https://www.nejm.org/doi/abs/10.1056/NEJMoa2204619?ref=theamericanquorum.com).

## Targeting a mutation once considered inaccessible

KRAS is among the most frequently altered cancer genes. The G12C substitution locks a portion of the signaling protein in a state that promotes tumor growth, and medicinal chemists have developed molecules that bind a pocket exposed when the mutant protein is inactive. Adagrasib is designed to bind KRAS G12C irreversibly and selectively, keeping the mutant protein in its inactive, GDP-bound state.

The development is important because KRAS mutations occur in a substantial share of lung adenocarcinomas, and the G12C variant is found in roughly 13% of those tumors. A [NEJM editorial](https://www.nejm.org/doi/full/10.1056/NEJMe2207902?ref=theamericanquorum.com) accompanying the clinical data described KRAS G12C inhibition as a new benchmark in a molecular subgroup for which direct targeted treatment had historically been elusive.

KRYSTAL-1 enrolled patients with advanced solid tumors carrying the mutation. The [trial record](https://clinicaltrials.gov/study/NCT03785249?a=10&tab=history&ref=theamericanquorum.com) documents the Phase 1/2 design, sequential dose exploration and expansion cohorts that ultimately supported the lung-cancer application. The approved dose is 600 milligrams by mouth twice daily until disease progression or unacceptable toxicity.

## Responses are meaningful, but accelerated approval is conditional

The 42.9% response rate establishes antitumor activity in a heavily pretreated population, but it does not answer every question about long-term benefit. Accelerated approval allows FDA to act on a surrogate or intermediate clinical endpoint reasonably likely to predict benefit for serious diseases with unmet need. Continued approval can depend on confirmatory evidence measuring outcomes such as progression-free or overall survival.

In the published cohort, median progression-free survival was 6.5 months and median overall survival was 12.6 months as of the study cutoffs. Treatment-related adverse events were common, with grade 3 or higher events reported in 44.8% of patients. Dose interruption and reduction were also frequent, reflecting the need to manage gastrointestinal effects, liver-test abnormalities and other toxicities during treatment.

Central nervous system disease is another important issue in advanced lung cancer. The study reported intracranial responses in a subgroup with previously treated, stable brain metastases, although the dataset was smaller and interpretation is more limited. A [September correspondence](https://www.nejm.org/doi/full/10.1056/NEJMc2210539?ref=theamericanquorum.com) in NEJM discussed those intracranial findings and the constraints of post hoc analysis.

## Companion diagnostics are part of the approval

Krazati is not intended for empiric use in all non-small-cell lung cancers. Patients must have a tumor with the KRAS G12C alteration identified by an FDA-approved test. The agency simultaneously approved diagnostic pathways that can detect the mutation in tissue or circulating tumor DNA.

The [Agilent Resolution ctDx FIRST](https://www.fda.gov/medical-devices/recently-approved-devices/agilent-resolution-ctdx-first-p210040?ref=theamericanquorum.com) assay can analyze cell-free DNA in blood and identify patients who may benefit from adagrasib. If a plasma test does not find the mutation, tumor tissue may still need to be assessed because circulating DNA tests can miss alterations when a tumor is not shedding enough DNA into the bloodstream.

QIAGEN also announced FDA approval of its [therascreen KRAS RGQ PCR kit](https://corporate.qiagen.com/English/newsroom/press-releases/press-release-details/2022/QIAGEN-receives-FDA-approval-for-companion-diagnostic-to-Mirati-Therapeutics-KRAZATI-in-non-small-cell-lung-cancer/default.aspx?ref=theamericanquorum.com) as a tissue-based companion diagnostic for Krazati. The pairing of a targeted drug with validated testing is a central feature of precision oncology: the treatment’s value depends on reliably identifying the molecular subgroup in which the drug’s mechanism is relevant.

## A second entrant changes the KRAS G12C treatment landscape

FDA previously granted accelerated approval to sotorasib for KRAS G12C-mutated NSCLC, so adagrasib enters a field with an existing targeted option rather than an empty market. The presence of two inhibitors creates new clinical questions involving efficacy, toxicity, sequencing, resistance and activity in patients with brain metastases.

The drugs also highlight a broader shift in lung-cancer care. Histology remains important, but treatment is increasingly organized around molecular drivers that can be measured and attacked directly. EGFR, ALK, ROS1, BRAF, MET, RET and other alterations already define treatment pathways for selected patients. KRAS, once seen largely as a marker of poor targetability, is now joining that list for the G12C subgroup.

For patients who have progressed after prior therapy, Krazati offers another oral targeted option with substantial response activity, but not a guarantee of durable disease control. The accelerated-approval framework explicitly recognizes that distinction. The immediate evidence supports tumor shrinkage in a defined molecular population; the longer-term task is to establish how much that translates into extended survival and improved quality of life, and how best to manage the toxicity that accompanies sustained KRAS inhibition.