====== KRYSTAL-1 ======

**KRYSTAL-1** is a Phase 1/2 clinical trial investigating the selective KRAS G12C inhibitor **adagrasib (MRTX849)** in patients with advanced solid tumors.

===== 🔬 General Information =====
  * **Drug:** Adagrasib (MRTX849)
  * **Trial Phase:** Phase 1/2
  * **Target Mutation:** KRAS G12C
  * **Tumor Types Studied:**
    * Colorectal Cancer (CRC)
    * Non-Small Cell Lung Cancer (NSCLC)
    * Other solid tumors

===== 🧪 Results in Colorectal Cancer (CRC) =====

==== Adagrasib Monotherapy ====
  * **Objective Response Rate (ORR):** 19%
  * **Median Progression-Free Survival (PFS):** 5.6 months
  * **Median Overall Survival (OS):** 19.8 months

==== Adagrasib + Cetuximab Combination ====
  * **ORR:** 34%
  * **Disease Control Rate (DCR):** 85.1%
  * **Median Duration of Response:** 5.8 months
  * **Median PFS:** 6.9 months
  * **Median OS:** 15.9 months
  * **Grade 3–4 Treatment-Related Adverse Events:** 27.7%
  * **Grade 5 Events:** None reported

===== 🫁 Results in Non-Small Cell Lung Cancer (NSCLC) =====
  * **ORR:** 43%
  * **Median Duration of Response:** 8.5 months
  * **Median PFS:** 6.5 months
  * **Median OS:** 12.6 months

===== ✅ Regulatory Update =====
  * In **June 2024**, the **FDA granted accelerated approval** for the combination of adagrasib + cetuximab in patients with previously treated KRAS G12C-mutant metastatic CRC.

===== 📚 Sources =====
  * [[https://www.nejm.org/doi/full/10.1056/NEJMoa2204619|NEJM article on NSCLC arm]]
  * [[https://pubmed.ncbi.nlm.nih.gov/38587856/|PubMed: CRC data]]
  * [[https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-adagrasib-cetuximab-kras-g12c-mutated-colorectal-cancer|FDA approval notice (2024)]]