A Phase Ii Study Of The Selective Met Kinase Inhibitor Inc280 In Advanced Papillary Renal Cell Cancer.

5075 Background: There are currently no approved systemic agents for patients with advanced type 1 papillary renal cell carcinoma (pRCC). Type 1 pRCC can occur in a hereditary form with germline alterations of MET (hereditary papillary RCC: HPRC) or in a sporadic form. Both hereditary and sporadic forms have similar histologic features and somatic MET alterations have been found in 15-20% of patients with sporadic pRCC. Furthermore, gain of chromosome 7, where MET and the gene for its ligand HGF are located, has been reported in a majority of patients with type 1 pRCC and may represent an alternative means of activating the MET pathway. This is a phase II study evaluating the activity of INC280, a highly selective and potent MET inhibitor, in patients with pRCC. Methods: Patients with advanced type 1 pRCC were treated with INC280 at a starting dose of 600mg PO twice daily (capsules). Later in the study course, the capsules were replaced with exposure-equivalent tablets (400mg PO twice daily). Eligible patients had an ECOG PS 0-2, no active brain metastases, and less than 4 prior lines of therapy. The primary endpoint was overall response rate (ORR) assessed by RECIST 1.1. Secondary endpoints included progression-free survival, disease control rate, and tolerability. Exploratory endpoints included the correlation between MET alteration/copy number gain and response to INC280. Results: Twenty subjects were enrolled from January 2014 to October 2019. Median age was 62 years, 60% of patients were classified as IMDC good risk and 40% as IMDC intermediate risk. Three patients (15%) achieved a confirmed partial response and seven (35%) had stable disease, including 4 (20%) who maintained stable disease for over 6 months. The most common treatment-related adverse events (AEs) were of grade 1-2 including nausea (85%), increased creatinine(70%) diarrhea(60%), fatigue(55%), limb edema(40%), increase in amylase(20%), triglycerides(20%), LFTs(20%), lipase(10%) and leukopenia(10%). INC280-related Grade 3-4 AEs included asymptomatic increased lipase (20%), increased LFTs (10%), increased amylase(5%), leukopenia (5%), lymphopenia (5%) and syncope (5%). Conclusions: INC280 demonstrated clinical activity in patients with advanced type 1 pRCC with an acceptable toxicity profile. The correlation between the presence of MET alteration and/or copy number gain and response to INC280 is under evaluation.