Phase Ib study of afatinib plus standard-dose cetuximab in patients (pts) with advanced solid tumors.

2536 Background: Afatinib combined with cetuximab has shown activity in pts with EGFRmutation-positive NSCLC and acquired resistance to EGFR tyrosine kinase inhibitors. Targeting the ErbB pathway may also be beneficial in other tumor types; for example, squamous cancers have high levels of EGFR overexpression. This Phase Ib study assessed afatinib plus standard-dose cetuximab in pts with other advanced solid tumors. Methods: In Part A, a 3+3 design was used to determine the maximum tolerated dose (MTD) of afatinib (from 30 to 40 mg daily) plus cetuximab (400 mg/m2 loading dose followed by 250 mg/m2weekly). Treatment was administered until disease progression or unacceptable toxicity. Dose-limiting toxicities (DLTs) in cycle 1 were used to determine MTD. In Part B, MTD was assessed in 3 expansion cohorts (squamous NSCLC, squamous cell carcinoma of head and neck [HNSCC], other tumors). Results: In Part A, 3 pts received afatinib 30 mg in cohort 1, and 6 received afatinib 40 mg in cohort 2. No DLTs were obse...