# Adagrasib

Source: https://onco.cc/drugs/adagrasib/  
OnCo record `adagrasib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adagrasib was the second KRAS G12C inhibitor, with a long half-life and brain penetration, and is approved in lung and colorectal cancer.

## Summary

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.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-04
- Brand: Krazati
- Modality: Small-molecule inhibitor (KRAS G12C)
- Mechanism: Covalent KRAS G12C inhibitor, 24-hour half-life.
- Approvals: 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); US 2024: KRAS G12C-mutated locally advanced or metastatic colorectal cancer after fluoropyrimidine, oxaliplatin and irinotecan chemotherapy, with cetuximab
- Dosing: Oral; 600 mg twice daily; with cetuximab in colorectal cancer
- Toxicity (grade 3+): Diarrhoea 0.9%; Nausea 4.3%; Fatigue 7%; Vomiting 0.9%; Musculoskeletal pain 7%; Hepatotoxicity 10%; Renal impairment 6%; Dyspnoea 10%; Oedema 0%; QT prolongation 6%

## Notes

- Pancreatic cancer: the Krazati label (effective 25 March 2026) covers KRAS G12C lung and colorectal cancer only; the KRYSTAL-1 phase 2 cohort of other solid tumours reported responses in 7 of 21 pancreatic cancers (33.3 percent), a median duration of response of 5.3 months and progression-free survival of 7.4 months across the cohort (JCO 2023), which is the basis of the NCCN listing. No NICE or EMA pancreatic indication.
- Pancreatic ductal adenocarcinoma: KRYSTAL-1's solid-tumour cohort gave 7 responses among 21 KRAS G12C pancreatic patients (33.3%), with a median duration of response of 5.3 months across tumour types (Bekaii-Saab 2023).
- Colorectal cancer biomarkers: KRAS G12C, with cetuximab rather than alone, for the same adaptive EGFR reactivation reason (KRYSTAL-1).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Adagrasib
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Adagrasib
- Bekaii-Saab et al., adagrasib in KRAS G12C solid tumours, KRYSTAL-1 (JCO 2023): https://doi.org/10.1200/JCO.23.00434
- Krazati label (openFDA): indications: https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22KRAZATI%22
- FDA oncology approval notifications: https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancerhematologic-malignancies-approval-notifications

## Connected records

- biomarkers: [KRAS G12C](https://onco.cc/biomarkers/kras-g12c/), [RAS wild-type (extended KRAS and NRAS testing)](https://onco.cc/biomarkers/ras-wild-type/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [KRAS G12C-mutant colorectal cancer](https://onco.cc/cancers/kras-g12c-colorectal/), [KRAS G12C-mutant non-small-cell lung cancer](https://onco.cc/cancers/kras-g12c-nsclc/), [KRAS G12C-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-g12c-pdac/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [KRAS & RAS inhibitors](https://onco.cc/technologies/kras-inhibitors/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- companies: [Bristol Myers Squibb](https://onco.cc/companies/bms/)
- trials: [A Multicenter Phase 1b/2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations](https://onco.cc/trials/nct06412198/), [A Solid Tumor Study for Long Term Treatment of Cancer Patients Who Participated in Adagrasib Studies](https://onco.cc/trials/nct07415031/), [A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)](https://onco.cc/trials/nct06875310/), [Adagrasib + SRS for Patients With Metastatic KRAS G12C-mutated NSCLC With Untreated Brain Metastases](https://onco.cc/trials/nct06248606/), [Combination Therapies With Adagrasib in Patients With Advanced NSCLC With KRAS G12C Mutation](https://onco.cc/trials/nct05609578/), [Krascendo 1](https://onco.cc/trials/krascendo-1/), [KRYSTAL-12](https://onco.cc/trials/krystal-12/), [Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1](https://onco.cc/trials/nct03785249/), [Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS G](https://onco.cc/trials/nct04613596/), [Trial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)](https://onco.cc/trials/nct05853575/)
- key papers: [CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug](https://onco.cc/key-papers/paper-codebreak-200-lancet-2023/), [KRAS G12C metastatic colorectal cancer: specific features of a new emerging target population](https://onco.cc/key-papers/paper-schirripa-kras-g12c-metastatic-colorectal-clin-colorectal-cancer-2020/), [KRYSTAL-1: adagrasib in advanced solid tumours harbouring a KRAS G12C mutation, including pancreatic cancer](https://onco.cc/key-papers/paper-krystal-1-adagrasib-kras-g12c-solid-tumours-jco-2023/), [KRYSTAL-1: adagrasib with or without cetuximab in KRAS G12C-mutated colorectal cancer](https://onco.cc/key-papers/paper-krystal-1-crc-yaeger-nejm-2023/), [KRYSTAL-12 plain language summary: adagrasib for non-small-cell lung cancer with KRAS G12C mutations](https://onco.cc/key-papers/paper-krystal-12-plain-language-summary-future-oncol-2026/), [Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable](https://onco.cc/key-papers/paper-ostrem-kras-g12c-nature-2013/)
- roadmaps: [KRAS roadmap: undruggable → G12C → pan-RAS](https://onco.cc/roadmaps/kras-roadmap/), [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)
- pathways: [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [MicroRNAs in cancer](https://onco.cc/pathways/micrornas-in-cancer/), [Non-small cell lung cancer (KEGG map)](https://onco.cc/pathways/nsclc-signalling/), [Pancreatic cancer (KEGG map)](https://onco.cc/pathways/pancreatic-cancer-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- pairings: [KRAS G12C inhibitor + anti-EGFR antibody (colorectal)](https://onco.cc/pairings/kras-plus-egfr-crc/)
- people: [Ferdinandos Skoulidis](https://onco.cc/people/ferdinandos-skoulidis/), [Kevan M. Shokat](https://onco.cc/people/kevan-shokat/), [Pasi A. Jänne](https://onco.cc/people/pasi-janne/)
- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- ideas: [Covalent chemistry for the RAS mutations that still have no drug](https://onco.cc/ideas/idea-bio1-pan-ras-covalent-g12d/)
- terms: [KRAS mutation subtypes (G12C, G12D, G12V)](https://onco.cc/terms/kras-mutation-subtypes/)
- drugs: [Resolution ctDx FIRST](https://onco.cc/drugs/resolution-ctdx-first/)

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