Phase I safety and pharmacokinetics study of rovalpituzumab tesirine in Japanese patients with advanced, recurrent small cell lung cancer. (September 2019)

• Record Type: Journal Article
• Authors: Udagawa, Hibiki; Akamatsu, Hiroaki; Tanaka, Kentaro; Takeda, Masayuki; Kanda, Shintaro; Kirita, Keisuke; Teraoka, Shunsuke; Nakagawa, Kazuhiko; Fujiwara, Yutaka; Yasuda, Ikuko; Okubo, Sumiko; Shintani, Masayuki; Kosloski, Matthew P.; Scripture, Charity; Tamura, Tomohide; Okamoto, Isamu
• Is Part Of: Lung cancer. Volume 135(2019)
• Page Start: 145
• Page End: 150
• Publication Date: 2019-09
• Subjects: Small cell lung cancer -- Japanese -- DLL3 -- Antibody drug conjugate -- Phase I; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2019.07.025
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Rova-T exhibited toxicity which was generally manageable in Japanese patients. Thrombocytopenia was most frequent treatment-related hematological adverse event. Safety and PK of Rova-T were similar to previous studies in non-Japanese patients. Disease control rate was 56% in DLL3 high patients treated with 0.3 mg/kg Rova-T. Confirmed partial responses in 17% of DLL3 high patients at 0.3 mg/kg Rova-T. Abstract: Objectives: Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate that targets delta-like protein 3 (DLL3) on small cell lung cancer (SCLC) tumors, is internalized and releases the toxin pyrrolobenzodiazepine to induce cell death. This open label phase I study was the first study of Rova-T in Japanese patients. The aim of this study was to evaluate, safety, pharmacokinetics, and preliminary efficacy of Rova-T in Japanese patients with advanced recurrent SCLC. Materials and methods: Patients received Rova-T (0.2 or 0.3 mg/kg) by intravenous infusion on Day (D) 1 of each 6-week cycle for 2 doses and dexamethasone (8 mg BID oral) on D-1, D1, and D2 of each 6-week cycle. Retreatment with Rova-T was permitted for patients who tolerated their initial doses and then progressed after disease control (defined as stable disease or better) was observed for at least 12 weeks after their last dose of Rova-T. Results: Rova-T exhibited toxicity that was generally manageable in Japanese patients (N = 29). No dose-limiting toxicities were experienced. The most common treatment-related adverse events (≥25% of patients, all grades) were platelet count decreased, pleural effusion, peripheral edema, aspartate aminotransferase increased, white blood cell count decreased, neutrophil count decreased, alanine aminotransferase increased, hypoalbuminaemia, anemia and decreased appetite. Safety and pharmacokinetics exposures were similar to previous observations in non-Japanese populations. Per investigator assessment of DLL3 high patients, 17% (3/18) had confirmed partial responses, and the disease control rate was 56%, mPFS was 2.9 months, and mOS was 7.4 months. Conclusions: These preliminary data support further exploration of Rova-T treatment in Japanese patients with SCLC in global studies. This trial was registered with ClinicalTrials.gov as NCT03086239.