A phase Ia/Ib study of novel anti-ErbB3 monoclonal antibody,barecetamab (ISU104) in refractory solid cancers and monotherapy or in combination with cetuximab in recurrent or metastatic head and neck cancer |
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Authors: | Seyoung Seo Bhumsuk Keam Seong Hoon Shin Yee Soo Chae Tae Min Kim Lee Chun Park Seung-Beom Hong Myung-Ju Ahn Sung-Bae Kim |
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Institution: | 1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;2. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea;3. Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Republic of Korea;4. Department of Oncology/Hematology, Kyungpook National University Medical Center Biobank, Daegu, Republic of Korea;5. Research Center, ISU ABXIS Co., Ltd., Seongnam, Republic of Korea;6. Department of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea |
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Abstract: | We evaluated the safety, tolerability, pharmacokinetics and antitumor activity of barecetamab monotherapy and combination cetuximab therapy in patients with advanced solid cancers, especially head and neck cancer (HNC). Part 1 was a 3 + 3 dose-escalation study in which 15 patients received barecetamab at 1, 3, 5, 10 and 20 mg/kg intravenously (IV) on days 1 and 28 and weekly in patients with advanced solid cancer. Part 2 was a dose-expansion study including two patient groups with advanced HNC, including six patients receiving barecetamab at 20 mg/kg IV every 3 weeks and 12 patients receiving barecetamab and cetuximab (400 mg/m2 on day 1 followed by 250 mg/m2 every week). No dose-limiting toxicities (DLTs) were observed. Maximum serum target engagement was reached with trough levels of doses ≥3 mg/kg IV weekly. Common adverse drug reactions were diarrhea, stomatitis, dermatitis acneiform and decreased appetite. One durable complete response of more than 17 months was observed, and the overall response and disease control rates were 36.4% (4/11) and 81.1% (9/11), respectively, in the combination therapy group. In conclusion, DLT was not observed in barecetamab at 1 to 20 mg/kg. The recommended phase II dose was determined to be 20 mg/kg triweekly. Barecetamab and in cetuximab combination was well tolerated and demonstrated meaningful antitumor effects. |
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Keywords: | barecetamab cetuximab ErbB3 head and neck cancer squamous cell carcinoma |
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