Phase I results of the randomized, placebo controlled, phase I/II study of the novel oral c-MET inhibitor, ARQ 197, irinotecan (CPT-11), and cetuximab (C) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) who have received front-line systemic therapy.

• DOI: 10.1200/jco.2011.29.15_suppl.3582
• Publication Date: 2017-02-23T13:58:03Z
• Authors: A. Bessudo; J. C. Bendell; N. Gabrail; M. V. Kopp; L. Mueller; L. L. Hart; V. I. Vladimirov; A. U. Pande; I. Gorbatchevsky; C. Eng
• Keywords: Tolerability

3582 Background: ARQ 197 selectively inhibits the c-MET receptor tyrosine kinase (RTK) which has been implicated in tumor cell migration, invasion, proliferation, and angiogenesis. CPT-11 plus C is a standard of care for CPT-11-refractory mCRC pts with WT KRAS tumors. Resistance to associated activation alternative RTK pathways including c-MET. We hypothesize that adding may decrease resistance therapy improve pt outcomes. Methods: The primary objectives phase I study were evaluate safety tolerability administered combination C, define recommended II dose (RPTD). Pts locally advanced or mCRC, who received > 1 prior line chemotherapy, ECOG performance status < 2 eligible. Cohorts 3 each treated (180 mg/m2) (500 every weeks along escalating doses (120, 240, 360 mg) PO BID. Blood tissue specimens collected PK, biomarker, other analyses. If no DLTs observed during first 28-day cycle all cohorts, mg BID would be defined as RPTD. Radiographic responses assessed 8 per RECIST v1.1. Results: Nine treated. Median age: 53 yr (range 30-77); PS 0/1: 4/5; median therapies: 1-4). No observed. To date, 4 have discontinued (2 disease progression, withdrew consent), 5 remain on duration 5.5 months (4.1-9.2). Reported grade 3/4 adverse events included: neutropenia (3/4: 0/1), fatigue 2/0), one case leucopenia, acneiform rash, vomiting, diarrhea, anemia syncope. Preliminary efficacy data 9 evaluable include CR (after cycles), PR SD, PD best response. Conclusions: was well tolerated encouraging preliminary antitumor activity previously patients. RPTD randomized portion continues accrual.