Chemorefractory KRAS G12C-mutated metastatic colorectal cancer — Amgen
Discover KOL Sentiment on CodeBreaK 300 →Design - Phase 3 sotorasib 960 mg + panitumumab vs standard of care (trifluridine/tipiracil or regorafenib), chemorefractory KRAS G12C mCRC (NCT05198934).
PFS (primary) - Median 5.6 vs 2.2 mo, HR 0.49 (95% CI 0.30-0.80), P=0.006; ORR 26% vs 0%.
OS - Immature/descriptive - median not estimable vs 10.3 mo, HR 0.70 (95% CI 0.41-1.18), P=0.20 (trend, not significant at interim).
Safety - Consistent with the component agents - sotorasib GI/hepatic events plus panitumumab skin/infusion reactions.
Regulatory - FDA approved January 16, 2025 - first targeted therapy for KRAS G12C mCRC after chemotherapy.
Sponsor / drugs - Amgen; sotorasib (Lumakras) + panitumumab (Vectibix).
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated July 21, 2026.
Top tweets by impressions — click to view on X
FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer
https://t.co/Ile5FhDjjX
#OCENewsBurst
$AMGN
The U.S Food and Drug Administration (FDA) extended the Prescription Drug User Fee Act (PDUFA) date for the Phase 3 CodeBreaK 300 study of LUMAKRAS plus Vectibix vs. investigator's choice of…
💊Final OS analysis of CodeBreak-300
@JCO_ASCO
➡️Sotorasib 960 + panitumumab vs. inv. choice
✅ORR: 30.2% vs 1.9%
✅mPFS: 5.6 vs 2 mo.
HR: 0.48 (0.30-0.78), p=.005
❓mOS: Not reached vs. 10.3 mo
HR:…
FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer
👉Based on CodeBreaK 300
👉mPFS 5.6 vs 2 mo, ORR 26% vs 0, no OS benefit most likely due to crossover
🧐Looking forward to…
Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator's Choice in Chemorefractory KRAS G12C Colorectal Cancer | Journal of Clinical Oncology…
🚨 FDA approves sotorasib + panitumumab for metastatic #colorectalcancer with KRAS G12C mutation 🚨
✅ Key results (CodeBreaK 300):
-Median PFS: 5.6 months vs. 2 months (standard treatment).
-ORR: 26%…
“Although not statistically significant, the observed OS HR and ORR along with prior PFS and safety findings support sotorasib 960 mg-panitumumab as a standard of care”
Spin alert 😵💫…
Tune in to hear @mgfakih of @cityofhope discuss the significance of this approval, key findings from the pivotal CodeBreaK 300 trial, and how this combination fits into the current KRAS G12C–mutated…
Phase III CodeBreaK 300: In chemorefractory KRAS G12C-mut mCRC, sotorasib 960mg + panitumumab improved PFS (5.7 vs 2.0 mo; HR 0.45) & ORR (30% vs 2%) vs SOC. OS trend favored combo (HR 0.70), but…
🧪 @SKamath_MD discusses exciting data from the CodeBreaK 300 trial along with @adasarimd and @doctorC369.
📺 The panel also discusses the use of ctDNA in adjuvant settings and sequencing challenges…
CodeBreaK 300 established sotorasib + panitumumab as the first FDA-approved targeted therapy for KRAS G12C-mutated mCRC after progression on chemotherapy. Biomarker-directed approach requires KRAS G12C testing. Complements BREAKWATER (BRAF V600E + anti-EGFR) in the growing landscape of genotype-directed mCRC regimens.
Median: 5.6 months (sotorasib 960 mg + panitumumab) vs. 2.2 months (SoC (trifluridine/tipiracil or regorafenib)). HR 0.49 (95% CI 0.30-0.80), P=0.006 Primary analysis (Fakih et al., NEJM 2023): median PFS 5.6 months with sotorasib 960 mg + panitumumab vs. 2.2 months with SoC (trifluridine/tipiracil or regorafenib); HR 0.49 (95% CI 0.30-0.80, P=0.006). Median follow-up 13.6 months at primary analysis. ORR 26% vs. 0% (SoC).
Median: NE (not estimable) (sotorasib 960 mg + panitumumab) vs. 10.3 months (SoC). HR 0.7 (95% CI 0.41-1.18), P=0.2 Overall survival descriptive analysis (per ASCO 2024 update slide): median OS not estimable with sotorasib 960 mg + panitumumab vs. 10.3 months with SoC; HR 0.70 (95% CI 0.41-1.18, P=0.20). Trend favoring the combination but did not reach statistical significance at interim. FDA approval (Jan 16, 2025) was based on the PFS and ORR benefit; OS data continue to mature.
Safety profile consistent with individual component agents — sotorasib GI and hepatic AEs combined with panitumumab skin/infusion AEs. Detailed Grade ≥3 TRAE rates pending full publication.
✅ First targeted therapy for KRAS G12C mCRC post-chemotherapy. CodeBreaK 300 established sotorasib + panitumumab as the first FDA-approved targeted therapy for KRAS G12C-mutated mCRC after progression on chemotherapy. Biomarker-directed approach requires KRAS G12C testing. Complements BREAKWATER (BRAF V600E + anti-EGFR) in the growing landscape of genotype-directed mCRC regimens.
CodeBreaK 300 is a Phase 3 randomized trial (NCT05198934) of sotorasib (Lumakras) 960 mg plus panitumumab versus investigator's choice standard of care (trifluridine/tipiracil or regorafenib) in patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer. Progression-free survival was the primary endpoint.
The sotorasib-plus-panitumumab combination significantly improved progression-free survival: median PFS was 5.6 versus 2.2 months (HR 0.49; 95% CI 0.30-0.80; P=0.006), with an objective response rate of 26% versus 0% for standard of care. Overall survival was descriptive and immature (median not estimable vs 10.3 months; HR 0.70; 95% CI 0.41-1.18; P=0.20), showing a trend favoring the combination that did not reach significance at interim.
Yes. On January 16, 2025 the FDA approved sotorasib (Lumakras) 960 mg with panitumumab (Vectibix) for KRAS G12C-mutated metastatic colorectal cancer, as determined by an FDA-approved test, in patients who have received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. It is the first FDA-approved targeted therapy for this molecular subtype.
Colorectal tumors adaptively reactivate EGFR signaling when KRAS G12C is inhibited alone, which blunts single-agent sotorasib activity. Adding the anti-EGFR antibody panitumumab blocks that feedback bypass, and CodeBreaK 300 confirmed the combination is substantially more active than either the KRAS inhibitor alone or standard of care in this setting.
Eligible patients have KRAS G12C-mutated metastatic colorectal cancer (confirmed by an FDA-approved test) whose disease has progressed after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. KRAS G12C testing is required to identify candidates for this biomarker-directed approach.
