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Sotorasib

Sotorasib (Lumakras) was the first drug to hit KRAS, approved in 2021 after four decades of failure.

CodeBreaK 100 (NSCLC ORR 37%), CodeBreaK 200 (PFS vs docetaxel), CodeBreaK 300 (with panitumumab in colorectal cancer, approved January 2025). Full approval in NSCLC pending confirmatory data.

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Sotorasib
PubChem
Mechanism, step by step
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1.Oral drug is absorbed and reaches the tumour

Modality
Small-molecule inhibitor (KRAS G12C)
Mechanism
Covalent binder to cysteine-12 in the switch-II pocket, locking KRAS G12C in the inactive GDP state.
Brand / code
Lumakras
Dosing & schedule
Route
Oral
Schedule
960 mg once daily (240 mg daily is the label-optional lower dose in NSCLC); with panitumumab in colorectal cancer
Dose modifications
Hold for grade ≥3 hepatotoxicity; discontinue for ILD
Monitoring
LFTs every 3 weeks for 3 months then monthly; respiratory symptoms

Source: US prescribing information (DailyMed). Doses are for orientation; the current label governs.

Medicare
Part D (self-administered)

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).

Commercial insurance
covered with prior authorisation

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.

Cancer Drugs FundNICE TA781 · 2022SMC: accepted
Appraised for
KRAS G12C-mutated advanced NSCLC after 1 or more systemic therapies
Notes
The CDF period ended after CodeBreaK 200 showed a modest PFS gain; NICE's 2024 reappraisal did not recommend routine commissioning at the price offered. Check the current position.
Cancer Drugs Fund
Entered the Cancer Drugs Fund under a managed access agreement; check the current CDF list for whether it has since moved to routine commissioning.
NHS England
Routinely funded for the appraised indication (or via managed access)

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.

Regulatory

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  1. Dec 2020DesignationUS

    Breakthrough Therapy designation source

  2. 28 May 2021ApprovalUS

    Accelerated approval, KRAS G12C NSCLC after ≥1 therapy: first KRAS inhibitor source

  3. Dec 2023Complete response letterUS

    FDA declines full approval based on CodeBreaK 200; postmarketing dose study required source

  4. 16 Jan 2025ApprovalUS

    KRAS G12C colorectal cancer with panitumumab (CodeBreaK 300) source

Approvals

RegionYearIndication
US2021KRAS G12C NSCLC, previously treated (accelerated)
US2025KRAS G12C colorectal cancer with panitumumab

Safety

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Toxicity profile
Adverse eventAny gradeGrade 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.

Cost & access

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Cost & access
CountryReimbursement
United StatesMedicare Part D (oral); commercial plans per formulary, often with prior authorisation
United KingdomNICE: recommended via Cancer Drugs Fund for KRAS G12C NSCLC after platinum (TA781); later terminated then re-appraised

List prices are manufacturer or Medicare figures where publicly disclosed; net prices after rebates are usually lower. Reimbursement changes; check the payer.

Trials

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ClinicalTrials.gov · phase 2/3
refreshed 2026-09-06
34 studies10 recruiting29 Phase 25 Phase 3
Search “Sotorasib” on ClinicalTrials.gov →
Counts are from a name search and may include unrelated studies; up to 100 studies are summarised.

Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Sotorasib
intervention: Sotorasib
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

Key papers

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rctThe Lancet 2023changed practice
CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug

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.

rctNew England Journal of Medicine 2023changed practice
CodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancer

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 barely works in bowel cancer. Responses are still modest and short-lived compared with EGFR or ALK inhibitors in lung cancer.

reviewNew England Journal of Medicine 2021changed practice
FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high

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.

basicNature 2013
Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable

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.

Latest papers

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Literature trend134 papers in the last 12 months-3% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

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.

Connected

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