Study of ONO-4538 in Non-Squamous Non-Small Cell Lung Cancer (TASUKI-52)

A Multicenter, Randomized, Double-Blind Trial in Subjects With Non-Squamous Non-Small Cell Lung Cancer (TASUKI-52)

The purpose of study is to compare the efficacy and safety of ONO-4538 in combination with carboplatin, paclitaxel, and bevacizumab (ONO-4538 group) to placebo in combination with carboplatin, paclitaxel, and bevacizumab (placebo group) in chemotherapy-naïve subjects with stage IIIB/IV or recurrent non-squamous non-small cell lung cancer unsuitable for radical radiation in a multicenter, randomized, double-blind study.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: ONO-4538; Drug: Carboplatin; Drug: Paclitaxel; Drug: Bevacizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 550
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan
    • Chiba Clinical Site
  • Chiba, Japan
    • Chiba Clinical Site2
  • Fukui, Japan
    • Fukui Clinical site
  • Fukuoka, Japan
    • Fukuoka Clinical Site2
  • Fukuoka, Japan
    • Fukuoka Clinical Site3
  • Fukuoka, Japan
    • Fukuoka Clinical Site4
  • Fukuoka, Japan
    • Fukuoka Clinical site
  • Gifu, Japan
    • Gifu Clinical site
  • Gifu, Japan
    • Gifu Clinical Site2
  • Hiroshima, Japan
    • Hiroshima Clinical Site2
  • Hiroshima, Japan
    • Hiroshima Clinical Site
  • Kochi, Japan
    • Kochi Clinical Site
  • Kumamoto, Japan
    • Kumamoto Clinical site
  • Kyoto, Japan
    • Kyoto Clinical Site
  • Nagasaki, Japan
    • Nagasaki Clinical Site
  • Niigata, Japan
    • Niigata Clinical Site
  • Niigata, Japan
    • Niigata Clinical Site2
  • Okayama, Japan
    • Okayama Clinical Site2
  • Okayama, Japan
    • Okayama Clinical site
  • Osaka, Japan
    • Osaka Clinical Site3
  • Osaka, Japan
    • Osaka Clinical site
  • Tokushima, Japan
    • Tokushima Clinical Site
  • Toyama, Japan
    • Toyama Clinical Site
  • Toyama, Japan
    • Toyama Clinical Site2
  • Wakayama, Japan
    • Wakayama Clinical Site
  • Yamaguchi, Japan
    • Yamaguchi Clinical Site
  • Ōita, Japan
    • Oita Clinical Site
  • Aichi
    • Nagoya, Aichi, Japan
      • Aichi Clinical Site2
    • Nagoya, Aichi, Japan
      • Aichi Clinical Site3
    • Nagoya, Aichi, Japan
      • Aichi Clinical Site4
    • Nagoya, Aichi, Japan
      • Aichi Clinical Site
    • Toyoake, Aichi, Japan
      • Aichi Clinical Site
  • Aomori
    • Hirosaki, Aomori, Japan
      • Aomori Clinical Site2
    • Hirosaki, Aomori, Japan
      • Aomori Clinical Site
  • Chiba
    • Yachiyo, Chiba, Japan
      • Chiba Clinical Site
  • Ehime
    • Matsuyama, Ehime, Japan
      • Ehime Clinical Site
  • Fukuoka
    • Iizuka, Fukuoka, Japan
      • Fukuoka Clinical site
    • Kitakyushu, Fukuoka, Japan
      • Fukuoka Clinical site
    • Koga, Fukuoka, Japan
      • Fukuoka Clinical site
    • Kurume, Fukuoka, Japan
      • Fukuoka Clinical site
  • Fukushima
    • Kōriyama, Fukushima, Japan
      • Fukushima Clinical Site
  • Gunma
    • Ota, Gunma, Japan
      • Gunma Clinical Site
    • Shibukawa, Gunma, Japan
      • Gunma Clinical Site
  • Hokkaido
    • Asahikawa, Hokkaido, Japan
      • Hokkaido Clinical site
    • Sapporo, Hokkaido, Japan
      • Hokkaido Clinical Site2
    • Sapporo, Hokkaido, Japan
      • Hokkaido Clinical site
  • Hyogo
    • Akashi, Hyogo, Japan
      • Hyogo Clinical Site
    • Amagasaki, Hyogo, Japan
      • Hyogo Clinical Site
    • Himeji, Hyogo, Japan
      • Hyogo Clinical Site
    • Itami, Hyogo, Japan
      • Hyogo Clinical Site
    • Kobe, Hyogo, Japan
      • Hyogo Clinical Site
    • Nishinomiya, Hyogo, Japan
      • Hyogo Clinical Site
    • Takarazuka, Hyogo, Japan
      • Hyogo Clinical Site
  • Ibaraki
    • Higashiibaraki, Ibaraki, Japan
      • Ibaraki Clinical Site
    • Kasama, Ibaraki, Japan
      • Ibaraki Clinical Site
    • Tsuchiura, Ibaraki, Japan
      • Ibaraki Clinical Site
  • Ishikawa
    • Kanazawa, Ishikawa, Japan
      • Ishikawa Clinical Site
    • Kanazawa, Ishikawa, Japan
      • Ishikawa Clinical Site2
    • Kanazawa, Ishikawa, Japan
      • Ishikawa Clinical Site3
  • Iwate
    • Morioka, Iwate, Japan
      • Iwate Clinical Site
  • Kanagawa
    • Isehara, Kanagawa, Japan
      • Kanagawa Clinical Site
    • Kawasaki, Kanagawa, Japan
      • Kanagawa Clinical Site2
    • Kawasaki, Kanagawa, Japan
      • Kanagawa Clinical Site
    • Sagamihara, Kanagawa, Japan
      • Kanagawa Clinical Site
    • Yokohama, Kanagawa, Japan
      • Kanagawa Clinical Site
    • Yokohama, Kanagawa, Japan
      • Kanagawa Clinical Site2
    • Yokohama, Kanagawa, Japan
      • Kanagawa Clinical Site3
  • Kumamoto
    • Koshi, Kumamoto, Japan
      • Kumamoto Clinical site
  • Kyoto
    • Jōyō, Kyoto, Japan
      • Kyoto Clinical Site
  • Mie
    • Tsu, Mie, Japan
      • Mie Clinical Site
  • Miyagi
    • Natori, Miyagi, Japan
      • Miyagi Clinical Site
    • Sendai, Miyagi, Japan
      • Miyagi Clinical Site
  • Nagano
    • Matsumoto, Nagano, Japan
      • Nagano Clinical Site
  • Nagasaki
    • Ōmura, Nagasaki, Japan
      • Nagasaki Clinical Site
  • Nara
    • Ikoma, Nara, Japan
      • Nara Clinical Site
  • Niigata
    • Nagaoka, Niigata, Japan
      • Niigata Clinical Site
  • Oita
    • Beppu, Oita, Japan
      • Oita Clinical Site
    • Yufu, Oita, Japan
      • Oita Clinical Site
  • Osaka
    • Habikino, Osaka, Japan
      • Osaka Clinical site
    • Hirakata, Osaka, Japan
      • Osaka Clinical site
    • Kishiwada, Osaka, Japan
      • Osaka Clinical site
    • Osakasayama, Osaka, Japan
      • Osaka Clinical site
    • Sakai, Osaka, Japan
      • Osaka Clinical site
    • Toyonaka, Osaka, Japan
      • Osaka Clinical site
  • Osaka Clinical Site
    • Osaka, Osaka Clinical Site, Japan
      • Osaka Clinical Site2
  • Saga
    • Ureshino, Saga, Japan
      • Saga Clinical Site
  • Saitama
    • Hidaka, Saitama, Japan
      • Saitama Clinical site
    • Kitaadachi-gun, Saitama, Japan
      • Saitama Clinical site
  • Shimane
    • Izumo, Shimane, Japan
      • Shimane Clinical Site
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan
      • Shizuoka Clinical site
    • Sunto-gun, Shizuoka, Japan
      • Shizuoka Clinical site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan
      • Tokyo Clinical site
    • Bunkyo-ku, Tokyo, Japan
      • Tokyo Clinical Site2
    • Bunkyō-Ku, Tokyo, Japan
      • Tokyo Clinical Site2
    • Chuo-ku, Tokyo, Japan
      • Tokyo Clinical site
    • Chuo-ku, Tokyo, Japan
      • Tokyo Clinical Site2
    • Fuchū, Tokyo, Japan
      • Tokyo Clinical site
    • Itabashi-ku, Tokyo, Japan
      • Tokyo Clinical site
    • Kiyose, Tokyo, Japan
      • Tokyo Clinical site
    • Koto-ku, Tokyo, Japan
      • Tokyo Clinical site
    • Meguro, Tokyo, Japan
      • Tokyo Clinical site
    • Minato-ku, Tokyo, Japan
      • Tokyo Clinical site
    • Mitaka-shi, Tokyo, Japan
      • Tokyo Clinical site
    • Shibuya, Tokyo, Japan
      • Tokyo Clinical site
    • Shinjuku-Ku, Tokyo, Japan
      • Tokyo Clinical Site2
    • Shinjuku-Ku, Tokyo, Japan
      • Tokyo Clinical Site3
    • Shinjuku-ku, Tokyo, Japan
      • Tokyo Clinical site
    • Tachikawa, Tokyo, Japan
      • Tokyo Clinical site
  • Tottori
    • Yonago, Tottori, Japan
      • Tottori Clinical site
  • Yamaguchi
    • Iwakuni, Yamaguchi, Japan
      • Yamaguchi Clinical Site
• Korea, Republic of
  • Busan, Korea, Republic of
    • Busan Clinical Site
  • Daegu, Korea, Republic of
    • Daegu Clinical Site
  • Incheon, Korea, Republic of
    • Incheon Clinical Site
  • Seoul, Korea, Republic of
    • Seoul Clinical Site2
  • Seoul, Korea, Republic of
    • Seoul Clinical Site3
  • Seoul, Korea, Republic of
    • Seoul Clinical Site4
  • Seoul, Korea, Republic of
    • Seoul Clinical Site5
  • Seoul, Korea, Republic of
    • Seoul Clinical Site6
  • Seoul, Korea, Republic of
    • Seoul Clinical Site
  • Chungcheongbuk-do
    • Cheongju-si, Chungcheongbuk-do, Korea, Republic of
      • Chungcheongbuk-do Clinical Site
  • Gangwon-Do
    • Wŏnju, Gangwon-Do, Korea, Republic of
      • Gangwon-Do Clinical Site
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of
      • Gyeonggi-do Clinical Site2
    • Seongnam-si, Gyeonggi-do, Korea, Republic of
      • Gyeonggi-do Clinical Site
    • Suwon, Gyeonggi-do, Korea, Republic of
      • Gyeonggi-do Clinical Site
  • Gyeongsangnam-do
    • Jinju-si, Gyeongsangnam-do, Korea, Republic of
      • Gyeongsangnam-do Clinical Site
• Taiwan
  • Changhua, Taiwan
    • Changhua Clinical Site
  • Chiayi City, Taiwan
    • Chiayi Clinical Site
  • Kaohsiung, Taiwan
    • Kaohsiung Clinical Site2
  • Kaohsiung, Taiwan
    • Kaohsiung Clinical Site
  • Kaohsiung, Taiwan
    • Kaohsiung Clinical Site3
  • Taichung, Taiwan
    • Taichung Clinical Site
  • Tainan, Taiwan
    • Tainan Clinical Site
  • Taipei, Taiwan
    • Taipei Clinical Site2
  • Taipei, Taiwan
    • Taipei Clinical Site
  • Taoyuan, Taiwan
    • Taoyuan Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects with histologically- or cytologically-confirmed non-squamous non-small cell lung cancer
• Subjects who received a diagnosis of stage IIIB/IV or recurrent non-squamous non-small cell lung cancer unsuitable for radical radiation according to the UICC-TNM Classification (7th edition) with no prior systemic anticancer therapy
• Subjects with at least one measurable lesion by radiographic tumor assessments per RECIST 1.1 criteria
• Subjects who are able to provide tumor tissue specimens.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1

Exclusion Criteria:

• Subjects with known EGFR mutations, including deletions in exon 19 and exon 21 (L858R) substitution mutations.
• Subjects with known ALK translocations.
• Complication or history of severe hypersensitivity reactions to antibody products or platinum-containing compounds
• Subjects with autoimmune disease or known chronic or recurrent autoimmune disease.
• Subjects with multiple cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ONO-4538 group; ONO-4538: 360 mg solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Chemotherapy: Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.	Drug: ONO-4538; 360 mg solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.; Drug: Carboplatin; Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.; Drug: Paclitaxel; Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.; Drug: Bevacizumab; Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.
Placebo Comparator: Placebo group; Placebo: Placebo solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Chemotherapy: Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent. Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.	Drug: Carboplatin; Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.; Drug: Paclitaxel; Carboplatin at AUC 6 and Paclitaxel at 200 mg/m2 intravenously in every 3 weeks for up to 4 cycles and if deemed safe, Carboplatin and Paclitaxel may continue for up to a maximum of 6 cycles until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.; Drug: Bevacizumab; Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.; Drug: Placebo; Placebo solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) as Assessed by the Independent Radiology Review Committee (IRRC)	PFS (as assessed by the IRRC) will be calculated using the following formula : PFS (days) = "date when overall response is assessed as progressive disease (PD) or date of death (for any reason), whichever comes first" - "date of randomization" + 1. Please refer to the protocol, in this study, tumor response will be evaluated by CT, etc. according to the RECIST 1.1 criteria.	Approximately 32 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		Approximately 32 months
Objective Response Rate (ORR [as Assessed by the IRRC])	ORR represents the proportion of subjects whose best overall response was assessed as complete response (CR) or partial response (PR). Please refer to the protocol, in this study, tumor response will be evaluated by CT, etc. according to the RECIST 1.1 criteria.	Approximately 32 months
Disease Control Rate (DCR [as Assessed by the IRRC])	DCR represents the proportion of subjects whose best overall response was assessed as CR, PR, or stable disease (SD). Please refer to the protocol, in this study, tumor response will be evaluated by CT, etc. according to the RECIST 1.1 criteria.	Approximately 32 months
Duration of Response (DOR [as Assessed by the IRRC])	The lower and upper limits of 95% CI for the median are censored value in the both groups.	Approximately 32 months
Best Overall Response (BOR [as Assessed by the IRRC])		Approximately 32 months

Collaborators and Investigators

• Sponsor: Ono Pharmaceutical Co. Ltd
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Shigeru Takahashi, Ono Pharmaceutical Co. Ltd

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2017
• Primary Completion (Actual): February 10, 2020
• Study Completion (Actual): December 4, 2023

Study Registration Dates

• First Submitted: April 12, 2017
• First Submitted That Met QC Criteria: April 14, 2017
• First Posted (Actual): April 17, 2017

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Immune Checkpoint Inhibitors; Carboplatin; Paclitaxel; Nivolumab; Bevacizumab
• Other Study ID Numbers: ONO-4538-52

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No