PP059 Phase lb and pharmacokinetics study of alpelisib and capecitabine in patients with advanced solid tumors

ESMO Open

article

A.R. Lim¹  B.Y. Kim²  J.H. Kim¹  M.H. Hyun¹  K.H. Park¹  Y.H. Kim¹  S.H. Lee¹ 

[1] 1Division of Medical Oncology, Department of Internal Medicine, Korea University Anam Hospital;2Korea University Cancer Research Institute, Korea University College of Medicine

关键词: Alpelisib;    PIK3CA;    Phase Ib Study;   

DOI  :  10.1016/j.esmoop.2022.100731

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background: This phase Ib study was performed to demonstrate synergistic efficacy incombination capecitabine with alpleisib (phosphatidylinositol 3-kinase catalytic subunit p110a blockade) and determine the maximal tolerated dose (MTD) and recommended phase ll dose (RP2D) of this combination regimen in patients withadvanced solid tumors refractory to standard therapy. The safety profile, anti-tumoractivity, and pharmacokinetics (PK) were conducted.Methods: Dose escalation phases were conducted in patients with advanced colorectal cancers and breast cancers who were refractory to standard therapy regardlessof PIK3CA mutation. Patients were administered orally once daily alpelisib (200mgand 300mg) and twice daily capecitabine (850mg, 1000mg, 1250mg orally, days 1e14)every 3 weeks. Standard “3+3” dose escalation was used to define the MTD. Theeffect of alpelisib on the PK of capecitabine was assessed.Results: Patients with 7 colorectal cancer (2 PIK3CA mutation) and 6 breast cancer (6PIK3CA mutation) were enrolled. The first three patients in dose level 0 (alpelisib200mg twice daily, capecitabine 1000 mg/ m2 twice daily) had no dose-limitingtoxicities (DLTs). In dose level 1 (alpelisib increased to 300 mg daily), one of six patients had DLT (grade (Gr) 3 hyperglycemia). When dose level 2 (alpelisib 300mg twicedaily, capecitabine 1250 mg/m2 twice daily) was expanded to 4 patients, no patientshad DLTs. The combination of alpelisib 300mg twice daily, and capecitabine 1000 mg/m2 twice daily was declared as the MTD/RP2D in patients with advanced solid tumors. The most common AEs were Gr 2-3 hyperglycemia (61.5%) and Gr 2 diarrhea(30.8%). Frequent all-grade, treatment-related AEs included Gr 2 oral mucositis(23.1%), Gr2 nausea (23.1%), Gr 2 fatigue (15.4%), and Gr 2 hand-foot syndrome(15.4%). Antitumor activity was observed in patients with PIK3CA mutant breastcancer (3 partial response and 3 stable disease in 6 patients). Alpelisib exposure(Cmax and AUC 0-12) was unaffected by concomitant capecitabine. There were noclinically relevant drug-drug interactions observed between alpelisib andcapecitabine.Conclusions: The combination of alpelisib and capecitabine is generally tolerated,without pharmacokinetic interactions, and shows antitumor activity in patients withPIK3CA mutant advanced cancers.

【 授权许可】

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