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Adagrasib was the second KRAS G12C inhibitor, with a long half-life and brain penetration, and is approved in lung and colorectal cancer.
Adagrasib is a covalent KRAS G12C inhibitor with a 24-hour half-life and brain penetration, dosed at 600 mg twice daily to keep the target continuously occupied. It was approved in 2022 (accelerated) for previously treated KRAS G12C NSCLC on KRYSTAL-1, with KRYSTAL-12 as the randomised follow-on, and in 2024 with cetuximab for KRAS G12C colorectal cancer on the KRYSTAL-1 combination cohort. Mirati developed it and was acquired by Bristol Myers Squibb in 2024. Gastrointestinal toxicity is frequent (diarrhoea 70%, nausea 69%), with hepatotoxicity (37%) and QT prolongation (20%) also needing monitoring. Activity in brain metastases is the main argument for choosing it over sotorasib, but resistance still develops within months. For a newcomer: the second KRAS G12C pill, distinguished by its long action and brain reach.
Covalent KRAS G12C inhibitor, 24-hour half-life. 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 TA1076. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
| Date | Deal | Type | Upfront | Total | Source |
|---|---|---|---|---|---|
| 2023-10-08 | Mirati Therapeutics to Bristol Myers Squibb Adagrasib (Krazati) and MRTX1133 (KRAS G12D) | Acquisition | not disclosed | $4.8bn (plus a contingent value right of up to $1.0bn) | source |
The first phase 3 comparing KRAS G12C inhibitors head to head. Timing is a registry-based estimate. Source
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Breakthrough Therapy designation source
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 The confirmatory requirement was still open 3.8 years later, when the FDA's table was read. source
In combination with cetuximab for the treatment of adult patients with KRAS G12C mutated locally advanced or metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
Accelerated approval on a surrogate endpoint, with a confirmatory trial required. source
KRAS G12C colorectal cancer with cetuximab (accelerated) source
Full approval in NSCLC (KRYSTAL-12) source
In combination with cetuximab for the treatment of adult patients with KRAS G12C mutated locally advanced or metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
Withdrawn: the indication came off the label 2.3 years after its accelerated approval. source
| Region | Year | Indication |
|---|---|---|
| US | 2022 | KRAS G12C NSCLC (accelerated) |
| US | 2024 | KRAS G12C colorectal cancer with cetuximab |
| EU | 2024 | KRAS G12C NSCLC after ≥1 line; 5 Jan 2024 (conditional) · Conditional marketing authorisation |
| US | 2024 | KRAS G12C-mutated locally advanced or metastatic colorectal cancer after fluoropyrimidine, oxaliplatin and irinotecan chemotherapy, with cetuximab · Accelerated approval on 21 June 2024 on the KRYSTAL-1 colorectal cohort; KRYSTAL-10 is the confirmatory randomised trial. No NICE recommendation for colorectal cancer at September 2026. |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Diarrhoea | 70% | 0.9% |
| Nausea | 69% | 4.3% |
| Fatigue | 59% | 7% |
| Vomiting | 56% | 0.9% |
| Musculoskeletal pain | 41% | 7% |
| Hepatotoxicity | 37% | 10% |
| Renal impairment | 36% | 6% |
| Dyspnoea | 35% | 10% |
| Oedema | 32% | 0% |
| QT prolongation | 20% | 6% |
KRYSTAL-1 NSCLC. 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 | bmsaccesssupport.com |
| United Kingdom | NICE: appraisal for KRAS G12C NSCLC (2025) | not disclosed | - |
List prices are manufacturer or Medicare figures where publicly disclosed; net prices after rebates are usually lower. Reimbursement changes; check the payer.
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Useful for a patient offered adagrasib after chemotherapy or immunotherapy who wants the trial explained without jargon. It adds no new data; the primary KRYSTAL-12 publication and the trial page remain the reference for the numbers.
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.
Adagrasib joins sotorasib as a later-line option for KRAS G12C pancreatic cancer in guidelines; both drugs are the template for the G12D and pan-RAS inhibitors now in pancreatic trials.
Adagrasib plus cetuximab is an approved option for previously treated KRAS G12C colorectal cancer, alongside sotorasib plus panitumumab; monotherapy is not enough because EGFR signalling reactivates the pathway.
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:"Adagrasib" OR ABSTRACT:"Adagrasib" OR TITLE:"Krazati" OR ABSTRACT:"Krazati") 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 Adagrasib, 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 Krascendo 1, KRAS G12C, Non-small cell lung cancer (KEGG map), KRAS G12C-mutant pancreatic ductal adenocarcinoma.
Shares KRAS G12C inhibitor + anti-EGFR antibody (colorectal), KRAS G12C metastatic colorectal cancer: specific features of a new emerging target population, Covalent chemistry for the RAS mutations that still have no drug, RAS wild-type (extended KRAS and NRAS testing).
Shares KRAS G12C, Non-small cell lung cancer (KEGG map), KRAS G12C-mutant pancreatic ductal adenocarcinoma, KRAS G12C-mutant colorectal cancer.
Shares Covalent chemistry for the RAS mutations that still have no drug, Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable, KRAS roadmap: undruggable → G12C → pan-RAS, Pancreatic cancer (KEGG map).
Shares Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable, KRAS G12C, KRAS mutation subtypes (G12C, G12D, G12V), KRAS G12C-mutant pancreatic ductal adenocarcinoma.
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 Ferdinandos Skoulidis, CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug, KRAS G12C-mutant non-small-cell lung cancer, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall.