# KRYSTAL-1: adagrasib in advanced solid tumours harbouring a KRAS G12C mutation, including pancreatic cancer

Source: https://onco.cc/key-papers/paper-krystal-1-adagrasib-kras-g12c-solid-tumours-jco-2023/  
OnCo record `paper-krystal-1-adagrasib-kras-g12c-solid-tumours-jco-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adagrasib, the second KRAS G12C pill, shrank tumours in about a third of patients with pancreatic cancer and in two in five with bile duct cancer in this basket study, with disease control for several months.

## Summary

Phase 2 cohort of the KRYSTAL-1 trial in 64 patients with previously treated KRAS G12C-mutated solid tumours other than lung or colorectal cancer, treated with adagrasib 600 mg twice daily. The pancreatic cohort had 21 patients and the biliary tract cohort 12; other tumours included appendiceal, ovarian, endometrial and small bowel cancers.

In pancreatic cancer the objective response rate was about 33 percent, with median progression-free survival of 5.4 months and median overall survival of 8.0 months; in biliary tract cancer the response rate was about 42 percent. Treatment-related adverse events were mostly gastrointestinal and manageable with dose reduction.

## Fields

- Kind: Key paper
- Last checked: 2026-09-21
- Journal: Journal of Clinical Oncology
- Year: 2023
- DOI: 10.1200/JCO.23.00434
- Authors: Bekaii-Saab TS, Yaeger R, Spira AI, et al.
- Findings: Pancreatic cohort (21 patients): objective response about 33 percent, median progression-free survival 5.4 months, median overall survival 8.0 months.; Biliary tract cohort (12 patients): objective response about 42 percent.
- What it means: 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.
- Caveats: Small single-arm cohorts with a short follow-up; the pancreatic response rate has a wide confidence interval.; KRAS G12C is found in only 1 to 2 percent of pancreatic cancers.

## Sources

- J Clin Oncol 2023: https://doi.org/10.1200/JCO.23.00434
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37099736/

## Connected records

- cancers: [KRAS G12C-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-g12c-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- drugs: [Adagrasib](https://onco.cc/drugs/adagrasib/)
- trials: [Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1](https://onco.cc/trials/nct03785249/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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