Loading
Sotorasib (Lumakras) was the first drug to hit KRAS, approved in 2021 after four decades of failure.
Sotorasib is a covalent inhibitor that binds cysteine 12 in the switch-II pocket of mutant KRAS, locking KRAS G12C in its inactive GDP-bound state; it was the first drug to hit KRAS, approved in 2021 after four decades of failure. CodeBreaK 100 gave a 37% response rate in previously treated NSCLC, CodeBreaK 200 showed a progression-free survival advantage over docetaxel, and CodeBreaK 300 with panitumumab in colorectal cancer gave PFS 5.6 versus 2.2 months (HR 0.49), leading to approval in January 2025. The label dose is 960 mg daily, with 240 mg an optional lower dose in NSCLC; hepatotoxicity (25%, 12% grade 3 or higher) is the main concern. Full approval in NSCLC still awaits confirmatory data, and resistance emerges faster than with EGFR or ALK drugs. For a newcomer: proof that the 'undruggable' KRAS could be drugged, with modest but real benefit.
Covalent binder to cysteine-12 in the switch-II pocket, locking KRAS G12C in the inactive GDP state. Connects to KRAS.
1.Oral drug is absorbed and reaches the tumour
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance: how tumours escape each drug class · Lines of therapy.
Source: US prescribing information (DailyMed). Doses are for orientation; the current label governs.
Oral, self-administered, so it is a Part D drug: covered through a stand-alone Part D plan or Medicare Advantage drug benefit, usually on the specialty tier with 25 to 33% coinsurance until the annual cap ($2,000 in 2025, $2,100 in 2026).
Covered for FDA-labelled and NCCN-listed uses, but almost always behind prior authorisation confirming diagnosis, biomarker and line of therapy; dispensed through a specialty pharmacy. KRAS G12C by an approved test.
Part D out-of-pocket capped at $2,000 (2025) / $2,100 (2026). Medicare patients cannot use manufacturer co-pay cards; charity funds (PAN, HealthWell, CancerCare) and the Extra Help subsidy are the routes.
Sources: Medicare.gov: Drug coverage (Part D) · Medicare.gov: Costs for Medicare drug coverage (annual out-of-pocket cap). Not medical or financial advice; verify with your plan.
Sources: NICE TA781 · NHS England Cancer Drugs Fund list · SMC advice: sotorasib. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
The first phase 3 comparing KRAS G12C inhibitors head to head. Timing is a registry-based estimate. Source
Compare all products across the US, EU, UK, Japan, China and Australia →
Breakthrough Therapy designation source
Treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.
Accelerated approval, KRAS G12C NSCLC after ≥1 therapy: first KRAS inhibitor The confirmatory requirement was still open 5.3 years later, when the FDA's table was read. source
FDA declines full approval based on CodeBreaK 200; postmarketing dose study required source
KRAS G12C colorectal cancer with panitumumab (CodeBreaK 300) source
| Region | Year | Indication |
|---|---|---|
| US | 2021 | KRAS G12C NSCLC, previously treated (accelerated) |
| US | 2025 | KRAS G12C colorectal cancer with panitumumab |
| EU | 2022 | EU brand Lumykras · Conditional marketing authorisation |
| US | 2025 | KRAS G12C-mutated metastatic colorectal cancer after fluoropyrimidine, oxaliplatin and irinotecan chemotherapy, with panitumumab · Approved 16 January 2025 on CodeBreaK 300. CodeBreaK 301 is testing the first-line combination. No NICE recommendation for colorectal cancer at September 2026. |
| England (NICE) | 2022 | KRAS G12C mutation-positive locally advanced or metastatic non-small-cell lung cancer that has progressed on, or after intolerance of, platinum-based chemotherapy or PD-1/PD-L1 immunotherapy · TA781, published 30 March 2022, recommends sotorasib for use within the Cancer Drugs Fund only, under a managed access agreement, because the clinical evidence was uncertain. |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Diarrhoea | 42% | - |
| Musculoskeletal pain | 35% | - |
| Nausea | 26% | - |
| Fatigue | 26% | - |
| Hepatotoxicity | 25% | 12% |
| Cough | 20% | - |
| Vomiting | 17% | - |
| Interstitial lung disease | 2.2% | 1.1% |
CodeBreaK 100. Rates read from the US prescribing information. Blank cells mean the figure was not sourced, not that it is zero.
| Country | Reimbursement | List price | Assistance |
|---|---|---|---|
| United States | Medicare Part D (oral); commercial plans per formulary, often with prior authorisation | not disclosed | amgensupportplus.com |
| United Kingdom | NICE: recommended via Cancer Drugs Fund for KRAS G12C NSCLC after platinum (TA781); later terminated then re-appraised | not disclosed | - |
List prices are manufacturer or Medicare figures where publicly disclosed; net prices after rebates are usually lower. Reimbursement changes; check the payer.
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Sotorasib is a guideline-listed later-line option for the 1 to 2 percent of pancreatic cancers with KRAS G12C, and the proof that KRAS in pancreatic cancer is druggable; the larger opportunity lies with inhibitors of G12D and pan-RAS drugs.
Patients with KRAS G12C lung cancer that has progressed after chemo-immunotherapy can take an oral KRAS inhibitor instead of docetaxel and gain a somewhat longer time to progression with fewer severe side effects, but should understand that most tumours become resistant within a year and that survival is not improved. KRAS G12C testing is worthwhile, but first-generation inhibitors are a step rather than a cure; combinations and next-generation inhibitors are the active research fronts.
Patients with metastatic colorectal cancer carrying a KRAS G12C mutation (about 3-4% of cases) who have exhausted standard chemotherapy now have a targeted option that works far better than trifluridine-tipiracil or regorafenib. The higher sotorasib dose is clearly superior, and the EGFR antibody is essential because KRAS inhibition alone has little effect in bowel cancer. Responses are still modest and short-lived compared with EGFR or ALK inhibitors in lung cancer.
The dose on the label is often not the best dose for patients; it is the highest one that was tolerable for a few weeks. Project Optimus means new cancer drugs should arrive with evidence on dose, and it gives clinicians licence to consider dose reduction for toxicity. For older drugs, the evidence gap persists.
It defines the population the G12C inhibitors address and sets the baseline against which CodeBreaK 300 and KRYSTAL-1 are read.
The most frequently mutated oncogene in cancer stopped being undruggable, and patients with KRAS G12C lung and bowel cancers now have targeted pills. The approach, exploiting a mutation-created chemical handle and an inactive-state pocket, has become a template for other hard targets.
Query for this drug: (TITLE:"Sotorasib" OR ABSTRACT:"Sotorasib" OR TITLE:"Lumakras" OR ABSTRACT:"Lumakras") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Sotorasib, not a curated reading list.
Shares KRAS G12C inhibitor + anti-EGFR antibody (colorectal), Krascendo 1, KRAS G12C metastatic colorectal cancer: specific features of a new emerging target population, Ferdinandos Skoulidis.
Shares CodeBreaK 100 (pancreatic cancer cohort), Covalent chemistry for the RAS mutations that still have no drug, Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable, Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026).
Shares Krascendo 1, KRAS G12C, Non-small cell lung cancer (KEGG map), KRAS G12C-mutant pancreatic ductal adenocarcinoma.
Shares A Rollover Study Evaluating Sotorasib With or Without Panitumumab in Participants With KRAS p.G12C Mutation, Study of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb in Treatment-naïve Participants With Metastatic Colorectal, Pre-operative Targeted Treatments in Molecularly Selected Resectable Colorectal Cancer (UNICORN), CodeBreaK 300.
Shares KRAS G12C, Non-small cell lung cancer (KEGG map), KRAS G12C-mutant pancreatic ductal adenocarcinoma, KRAS G12C-mutant colorectal cancer.
Shares KRAS G12C-mutant pancreatic ductal adenocarcinoma, KRAS G12C-mutant colorectal cancer, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, KRAS & RAS inhibitors.
Shares Covalent chemistry for the RAS mutations that still have no drug, Drug discovery roadmap: screening in mice → maps of dependency → designing in silico, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, KRAS & RAS inhibitors.
Shares Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable, KRAS roadmap: undruggable → G12C → pan-RAS, KRAS mutation subtypes (G12C, G12D, G12V), The undruggable drivers.