FDA approves sotorasib plus panitumumab, the first KRAS G12C-targeted combination for colorectal cancer

Evidence stage: Later-Stage HumanRegulatory status: FDA-approved for the exact stated cancer/useGuideline status: Not addressed

The FDA approved sotorasib (Lumakras) in combination with panitumumab (Vectibix) for adults with KRAS G12C-mutated locally advanced or metastatic colorectal cancer who have received prior fluoropyrimidin-, oxaliplatin-, and irinotecan-based chemotherapy — the first FDA-approved KRAS G12C-targeted combination for this cancer type, and a biomarker-selected, precision-medicine approach that requires confirming the specific KRAS G12C mutation before treatment. The approval was based on the randomized, open-label, phase 3 CodeBreaK 300 trial (ClinicalTrials.gov NCT05198934; a 3-year overall-survival update presented at ASCO 2024, Journal of Clinical Oncology, DOI 10.1200/JCO.2024.42.17_suppl.LBA3510). In the analysis population supporting approval, sotorasib (960 mg daily) plus panitumumab (53 patients) achieved a median progression-free survival of 5.6 months versus 2.0 months with standard-of-care chemotherapy (54 patients; hazard ratio 0.48), and an objective response rate of 26% versus 0%.

What This Means

In the randomized, phase 3 CodeBreaK 300 trial, sotorasib plus panitumumab significantly extended progression-free survival (5.6 months vs 2.0 months, hazard ratio 0.48) and improved objective response rate (26% vs 0%) compared with standard-of-care chemotherapy, in patients whose colorectal cancer carries a specific KRAS G12C mutation and had already progressed on standard chemotherapy -- the first FDA-approved KRAS G12C-targeted combination for this cancer type.

What This Doesn't Mean

This approval REQUIRES confirming a KRAS G12C mutation via an FDA-approved test before treatment -- it does not apply to KRAS-wild-type or other KRAS-mutation colorectal cancers, and it is approved specifically for patients who have already received and progressed on standard chemotherapy, not as a first-line treatment.

Why It Matters

A biomarker-gated, targeted combination with a statistically significant efficacy benefit in a genomically defined subgroup of colorectal cancer represents real precision-medicine progress -- this record closes the "precision medicine" topic-breadth gap on this site and adds real depth to colorectal cancer coverage alongside this site's other colorectal-cancer records.

Promise & Proof

Proof — strength of the evidence 5 / 5
  • Base score from evidence stage: Later-Stage Human.
  • FDA-approved for the exact stated cancer/use.
Promise — potential significance if later evidence holds up 3 / 5
  • Baseline — a validly-evidenced story starts here; every further point below is an explicit, checkable reason.
  • The record includes substantive editorial reasoning about why this discovery matters.
  • A distinct follow-on/confirmatory study or trial is already cited as a secondary source — the field is already building on this finding.

These two ratings are automatically computed from this story's own structured evidence fields and are shown separately on purpose — they are never combined into one score. They describe this record, not a medical recommendation: they do not establish medical certainty, do not substitute for reading the cited sources, and are recalculated whenever the underlying evidence changes.

Population / Applicability

Studied in: Adults with KRAS G12C-mutated, locally advanced or metastatic colorectal cancer previously treated with fluoropyrimidin-, oxaliplatin-, and irinotecan-based chemotherapy, randomized to sotorasib (960 mg daily) plus panitumumab (53 patients) or investigator's choice of standard-of-care chemotherapy (54 patients), in the analysis population supporting FDA approval within the phase 3 CodeBreaK 300 trial. (Adults)

Requires KRAS G12C mutation testing by an FDA-approved companion diagnostic before use -- not a treatment option for the majority of colorectal cancers, which do not carry this specific mutation. This record has not independently reviewed the full safety/tolerability profile, which should be added before publication.

Full evidence details
Study design
Randomized controlled trial
Sample size
107

Funding & Conflicts

Sponsor/developer: Amgen Inc. -- not independently confirmed against a primary corporate-disclosure document.

Regulatory status by jurisdiction

United States (FDA)

Status
FDA-approved for the exact stated cancer/use
Indication
Adults with KRAS G12C-mutated locally advanced or metastatic colorectal cancer, as determined by an FDA-approved test, who have received prior fluoropyrimidin-, oxaliplatin-, and irinotecan-based chemotherapy.
Biomarker requirement
KRAS G12C mutation, as determined by an FDA-approved test
Decision date
2025-01-16
Source
Regulator record (opens in a new tab)

Guideline positions

Guideline

Position
Not addressed
Last verified
2026-08-13

Primary evidence supporting this story

Additional context

Why Should I Trust This?

  • 1 source at Tier 2 — Peer-reviewed primary research, trial registries, regulatory documents, official conference abstracts
  • Last reviewed: 2026-08-13

This panel summarizes real, checkable facts about this record's own sources and review status — it is not a trust score, and reading it is not a substitute for reading the cited sources yourself.

Discovery Timeline

Every recorded change to this record's content or publication status, in order.

  1. Status change — Status changed from "Legacy / Unverified" to "In editorial review".
  2. Status change — Status changed from "In editorial review" to "Verified".

Last reviewed

Related discoveries

FDA approves sotorasib plus panitumumab, the first KRAS G12C-targeted combination for colorectal cancer

https://cancerdiscoveries.com/discoveries/fda-approves-sotorasib-plus-panitumumab-the-first-kras-g12c-targeted-combination-for-colorectal-cancer/

Evidence stage: Later-Stage Human

What This Means

In the randomized, phase 3 CodeBreaK 300 trial, sotorasib plus panitumumab significantly extended progression-free survival (5.6 months vs 2.0 months, hazard ratio 0.48) and improved objective response rate (26% vs 0%) compared with standard-of-care chemotherapy, in patients whose colorectal cancer carries a specific KRAS G12C mutation and had already progressed on standard chemotherapy -- the first FDA-approved KRAS G12C-targeted combination for this cancer type.

What This Doesn't Mean

This approval REQUIRES confirming a KRAS G12C mutation via an FDA-approved test before treatment -- it does not apply to KRAS-wild-type or other KRAS-mutation colorectal cancers, and it is approved specifically for patients who have already received and progressed on standard chemotherapy, not as a first-line treatment.

Why It Matters

A biomarker-gated, targeted combination with a statistically significant efficacy benefit in a genomically defined subgroup of colorectal cancer represents real precision-medicine progress -- this record closes the "precision medicine" topic-breadth gap on this site and adds real depth to colorectal cancer coverage alongside this site's other colorectal-cancer records.

Primary sources

  • Overall survival (OS) of phase 3 CodeBreaK 300 study of sotorasib plus panitumumab (soto+pani) versus investigator's choice of therapy for KRAS G12C-mutated metastatic colorectal cancer (mCRC) (Journal of Clinical Oncology, ASCO Annual Meeting) — https://doi.org/10.1200/JCO.2024.42.17_suppl.LBA3510 (DOI 10.1200/JCO.2024.42.17_suppl.LBA3510)

Date verified: 2026-08-13

Correction status: No correction or retraction