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Patritumab, a human anti\u2010<jats:styled-content style=\"fixed-case\">HER<\/jats:styled-content>3 m<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>b, has shown anticancer activity in preclinical models. This study examined the safety and pharmacokinetics of patritumab in combination with trastuzumab and paclitaxel in patients with <jats:styled-content style=\"fixed-case\">HER<\/jats:styled-content>2\u2010overexpressing metastatic breast cancer. In this open\u2010label, multicenter, dose\u2010escalation, phase Ib study, patients received patritumab 9 or 18\u00a0mg\/kg plus trastuzumab and paclitaxel at known tolerated doses. Safety and tolerability were assessed based on dose\u2010limiting toxicities and other non\u2010life threatening adverse events. The pharmacokinetic profile for patritumab was determined based on the target trough level. Clinical efficacy was evaluated based on the overall response rate and progression\u2010free survival. Six patients received patritumab 9\u00a0mg\/kg and 12 received 18\u00a0mg\/kg. The most common adverse events were diarrhea, alopecia, leukopenia, neutropenia, and maculopapular rash. No dose\u2010limiting toxicities were observed. The target trough serum concentration was achieved in all patients at a dose of 18\u00a0mg\/kg. Overall response rate was 38.9% and median progression\u2010free survival was 274\u00a0days. In conclusion, patritumab plus trastuzumab and paclitaxel was tolerable and efficacious at both doses. We recommend the dose level of 18\u00a0mg\/kg for future phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> studies. 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