Dual targeting of @entity470 / @entity470 and XXXX with cetuximab and trastuzumab in @entity1 with metastatic @entity788 after @entity136 failure: results of the "THERAPY"phase 1-2 trial.

@entity1 @entity788 @entity137 @entity470 @entity136 @entity1722
To improve treatment efficacy, we decided to simultaneously target @entity470 and @entity1722 with trastuzumab and cetuximab. Following promising preclinical results, we conducted a phase 1-2 trial in advanced @entity788 @entity1 after first-line @entity136 -based chemotherapy failure. In this single-arm, non-randomized, multicenter trial, @entity1 received weekly cetuximab (400mg/m  , then 250mg/m  ). They were sequentially included in two trastuzumab dose levels: 3.0 or 4.0mg/kg, then 1.5 or 2.0mg/kg/weekly. Endpoints were the objective response rate, safety, progression-free (PFS) and overall survival (OS). During phase 1 (n=10 @entity1 ), @entity137 were evenly distributed except for @entity137 that frequently caused compliance issues. The higher dose level was defined as the trastuzumab recommended dose. During phase 2 (n=39 @entity1 ), @entity137 were mainly cutaneous reactions and asthenia. No objective response was observed. Nine @entity1 were stabilized but arrested treatment due to @entity137 . Median PFS was 1.8 months (95%CI: 1.7-2.0 months) and median OS was 4.6 months (95%CI: 2.7-6.6 months). Both were positively correlated with @entity137 severity (P=0.027 and P=0.001, respectively). Conventional phase 1 dose-escalation schedules are unsuitable for targeted therapies because most cutaneous @entity137 are not considered dose-limiting @entity137 . The compliance issues caused by @entity137 were particularly detrimental because of the @entity137 -response correlation.
