A Phase 2 Study of Savolitinib in Subjects With MET Amplified Metastatic Colorectal Cancer
This phase II trial studies how well savolitinib works in treating patients with MET amplified colorectal cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Savolitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic and/or unresectable
• Documented wild-type in KRAS and NRAS (codons 12, 13, 59, 61, 117, and 146) and in BRAF codon 600, based on tumor tissue taken from primary or metastatic site prior to anti-EGFR antibody treatment
• At least one site of disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• MET amplification detected by the Guardant360 circulating free deoxyribonucleic acid (cfDNA) screening assay (MET copy number \>= 2.2)
• Clinical or radiographic progression on treatments containing a fluoropyrimidine (e.g., 5- fluorouracil or capecitabine), oxaliplatin, irinotecan, and an anti-VEGF monoclonal antibody (bevacizumab, ziv-aflibercept) or anti-VEGFR monoclonal antibody (ramucirumab), and an anti-PD1 monoclonal antibody (nivolumab or pembrolizumab) for patients with microsatellite instability (MSI)-high/mismatch repair (MMR) deficient tumors, or the treatments were not tolerated or contraindicated
• Clinical or radiographic progression on prior anti-EGFR antibody therapy (either panitumumab or cetuximab)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky \>= 80%)
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Hemoglobin (Hgb) \>= 9 g/dL (no transfusion in the past 2 weeks)
• Platelets \>= 100,000/mcL (no transfusion in the past 10 days)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x the institutional upper limit of normal (ULN) with total bilirubin (TBL) =\< 1 x ULN OR
• Total bilirubin (TBL) \> ULN =\<1.5 × ULN with ALT and AST =\< 1x ULN
• Glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2
• International normalization ratio (INR) \< 1.5 x ULN and activated partial thromboplastin time (aPTT) \< 1.5 x ULN unless patients are receiving therapeutic anticoagulation which affects these parameters
• Females of childbearing potential should be willing to use adequate contraceptive measures, should not be breast feeding, and must have a negative pregnancy test if of childbearing potential or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
⁃ Post-menopausal is defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments; women under the age of 50 years would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution; or women with documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• Male patients with female partner of childbearing potential should be willing to use barrier contraception during the study and for 6 months following discontinuation of study drug
• Ability to swallow and retain oral medications
• Ability to understand and the willingness to sign a written informed consent document