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PURPOSE: This phase I dose-escalation study investigated the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of CH5132799. EXPERIMENTAL DESIGN: Patients with metastatic solid tumors were eligible for the study. CH5132799 was administered orally once daily or twice daily in 28-day cycles. RESULTS: Thirty-eight patients with solid tumors received CH5132799 at 2 to 96 mg once daily or 48 to 72 mg twice daily. The MTD was 48 mg on the twice-daily schedule but was not reached on the once daily schedule. DLTs were grade 3 elevated liver function tests (LFT), grade 3 fatigue, grade 3 encephalopathy, grade 3 diarrhea, and grade 3 diarrhea with grade 3 stomatitis; all DLTs were reversible. Most drug-related adverse events were grade 1/2. Diarrhea (34%) and nausea (32%) were the most common events. Mean Cmax and AUC0-24 in steady state at MTD were 175 ng/mL and 1,550 ng·h/mL, respectively, consistent with efficacious exposure based on preclinical modeling. Reduction in SUVmax with [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET) was observed in 5 of 7 patients at MTD. A patient with PIK3CA-mutated clear cell carcinoma of the ovary achieved a partial response by GCIG CA125 criteria and further, a heavily pretreated patient with triple-negative breast cancer had marked improvement in her cutaneous skin lesions lasting six cycles. CONCLUSION: CH5132799 is well tolerated at the MTD dose of 48 mg twice daily. At this dose, the drug had a favorable PK and PD profile and preliminary evidence of clinical activity.

Original publication




Journal article


Clin Cancer Res

Publication Date





5908 - 5917


Administration, Oral, Adult, Aged, Antineoplastic Agents, Class I Phosphatidylinositol 3-Kinases, Dose-Response Relationship, Drug, Female, Humans, Male, Maximum Tolerated Dose, Middle Aged, Neoplasm Metastasis, Neoplasms, Positron-Emission Tomography, Pyrimidines, Sulfonamides, Tomography, X-Ray Computed, Treatment Outcome