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

Hibiki Udagawa, Hiroaki Akamatsu, Kentaro Tanaka, Masayuki Takeda, Shintaro Kanda, Keisuke Kirita, Shunsuke Teraoka, Kazuhiko Nakagawa, Yutaka Fujiwara, I. Yasuda, Sumiko Okubo, Masayuki Shintani, Matthew P. Kosloski, Charity Scripture, Tomohide Tamura, Isamu Okamoto

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)145-150
Number of pages6
JournalLung Cancer
Volume135
DOIs
Publication statusPublished - Sep 1 2019

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Small Cell Lung Carcinoma
Pharmacokinetics
Safety
Hypoalbuminemia
Retreatment
Appetite
Pleural Effusion
Aspartate Aminotransferases
Alanine Transaminase
Platelet Count
Leukocyte Count
Intravenous Infusions
Dexamethasone
Anemia
Edema
Neutrophils
Cell Death
Research Personnel
Antibodies
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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Phase I safety and pharmacokinetics study of rovalpituzumab tesirine in Japanese patients with advanced, recurrent small cell lung cancer. / Udagawa, Hibiki; Akamatsu, Hiroaki; Tanaka, Kentaro; Takeda, Masayuki; Kanda, Shintaro; Kirita, Keisuke; Teraoka, Shunsuke; Nakagawa, Kazuhiko; Fujiwara, Yutaka; Yasuda, I.; Okubo, Sumiko; Shintani, Masayuki; Kosloski, Matthew P.; Scripture, Charity; Tamura, Tomohide; Okamoto, Isamu.

In: Lung Cancer, Vol. 135, 01.09.2019, p. 145-150.

Research output: Contribution to journalArticle

Udagawa, H, Akamatsu, H, Tanaka, K, Takeda, M, Kanda, S, Kirita, K, Teraoka, S, Nakagawa, K, Fujiwara, Y, Yasuda, I, Okubo, S, Shintani, M, Kosloski, MP, Scripture, C, Tamura, T & Okamoto, I 2019, 'Phase I safety and pharmacokinetics study of rovalpituzumab tesirine in Japanese patients with advanced, recurrent small cell lung cancer', Lung Cancer, vol. 135, pp. 145-150. https://doi.org/10.1016/j.lungcan.2019.07.025
Udagawa, Hibiki ; Akamatsu, Hiroaki ; Tanaka, Kentaro ; Takeda, Masayuki ; Kanda, Shintaro ; Kirita, Keisuke ; Teraoka, Shunsuke ; Nakagawa, Kazuhiko ; Fujiwara, Yutaka ; Yasuda, I. ; Okubo, Sumiko ; Shintani, Masayuki ; Kosloski, Matthew P. ; Scripture, Charity ; Tamura, Tomohide ; Okamoto, Isamu. / Phase I safety and pharmacokinetics study of rovalpituzumab tesirine in Japanese patients with advanced, recurrent small cell lung cancer. In: Lung Cancer. 2019 ; Vol. 135. pp. 145-150.
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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.",
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T1 - Phase I safety and pharmacokinetics study of rovalpituzumab tesirine in Japanese patients with advanced, recurrent small cell lung cancer

AU - Udagawa, Hibiki

AU - Akamatsu, Hiroaki

AU - Tanaka, Kentaro

AU - Takeda, Masayuki

AU - Kanda, Shintaro

AU - Kirita, Keisuke

AU - Teraoka, Shunsuke

AU - Nakagawa, Kazuhiko

AU - Fujiwara, Yutaka

AU - Yasuda, I.

AU - Okubo, Sumiko

AU - Shintani, Masayuki

AU - Kosloski, Matthew P.

AU - Scripture, Charity

AU - Tamura, Tomohide

AU - Okamoto, Isamu

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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.

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