P-79 C-PRECISE-01 study: A phase Ib/II trial of MEN1611, a PI3K inhibitor, and cetuximab in patients with PIK3CA mutated metastatic colorectal cancer failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens

Abstract

MEN1611 (MEN) is an oral PI3K inhibitor active on the p110α (mutants and wild type), β and γ isoforms while sparing the δ. Preclinical and clinical evidence supports the development of MEN1611 in combination with other agents in the context of solid tumors. The presence of PIK3CA mutations in mCRC has been reported to correlate with a negative prediction of response to anti-EGFR treatment, making PI3K an attractive therapeutic target. C-PRECISE-01 is an open-label, multicentre, phase Ib/II study of MEN1611, a PI3K Inhibitor, and cetuximab in patients with PIK3CA mutated, RAS and RAF wild-type metastatic colorectal cancer (mCRC) failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens. N-K-RAS, BRAF and PIK3CA mutations will be detected in ctDNA assay during pre-screening period and centrally analysed using a validated test. A dose-confirmation (Step 1) and cohort expansion (Step 2) design combines 2 dose levels (48 mg and 32 mg) of oral MEN BID for continuous 28-day cycles and weekly IV infusions of cetuximab until objective disease progression is documented or another criterion for discontinuation is met. After the completion of Step 1, the study will continue in an expansion cohort (Step 2) testing the Recommended phase 2 dose (RP2D) in a total of 40 evaluable patients. The primary study objectives are to determine combination RP2D (step 1) and to assess the antitumor activity (step 2). Secondary objectives include the assessment of safety, tolerability and pharmacokinetics profile of MEN1611 in combination with cetuximab. Adverse events will be collected and graded according to NCI CTCAE version 5.0. Responses will be evaluated according to RECIST v1.1. All study variables (with the exception of PK variables) will be presented by dose cohort and overall, using the appropriate descriptive statistics. The enrolment is expected to start in Q2/Q3 2020 at US and European sites. Menarini Ricerche S.p.A.