MedPath

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

Phase 3
Completed
Conditions
Non-Small Cell Lung Cancer
Interventions
Registration Number
NCT03117049
Lead Sponsor
Ono Pharmaceutical Co. Ltd
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
550
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ONO-4538 groupONO-4538ONO-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.
Placebo groupBevacizumabPlacebo: 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.
Placebo groupPlaceboPlacebo: 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.
ONO-4538 groupCarboplatinONO-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.
ONO-4538 groupPaclitaxelONO-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.
ONO-4538 groupBevacizumabONO-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.
Placebo groupCarboplatinPlacebo: 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.
Placebo groupPaclitaxelPlacebo: 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.
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) as Assessed by the Independent Radiology Review Committee (IRRC)Approximately 32 months

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.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)Approximately 32 months
Best Overall Response (BOR [as Assessed by the IRRC])Approximately 32 months
Disease Control Rate (DCR [as Assessed by the IRRC])Approximately 32 months

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.

Duration of Response (DOR [as Assessed by the IRRC])Approximately 32 months

The lower and upper limits of 95% CI for the median are censored value in the both groups.

Objective Response Rate (ORR [as Assessed by the IRRC])Approximately 32 months

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.

Trial Locations

Locations (84)

Chungcheongbuk-do Clinical Site

🇰🇷

Cheongju-si, Chungcheongbuk-do, Korea, Republic of

Aichi Clinical Site

🇯🇵

Toyoake, Aichi, Japan

Aichi Clinical Site2

🇯🇵

Nagoya, Aichi, Japan

Aichi Clinical Site3

🇯🇵

Nagoya, Aichi, Japan

Aomori Clinical Site2

🇯🇵

Hirosaki, Aomori, Japan

Aomori Clinical Site

🇯🇵

Hirosaki, Aomori, Japan

Gunma Clinical Site

🇯🇵

Shibukawa, Gunma, Japan

Hokkaido Clinical Site2

🇯🇵

Sapporo, Hokkaido, Japan

Ishikawa Clinical Site3

🇯🇵

Kanazawa, Ishikawa, Japan

Ishikawa Clinical Site

🇯🇵

Kanazawa, Ishikawa, Japan

Kanagawa Clinical Site

🇯🇵

Yokohama, Kanagawa, Japan

Kanagawa Clinical Site3

🇯🇵

Yokohama, Kanagawa, Japan

Nagano Clinical Site

🇯🇵

Matsumoto, Nagano, Japan

Niigata Clinical Site

🇯🇵

Niigata, Japan

Osaka Clinical Site2

🇯🇵

Osaka, Osaka Clinical Site, Japan

Saga Clinical Site

🇯🇵

Ureshino, Saga, Japan

Shizuoka Clinical Site

🇯🇵

Sunto-gun, Shizuoka, Japan

Fukuoka Clinical Site3

🇯🇵

Fukuoka, Japan

Niigata Clinical Site2

🇯🇵

Niigata, Japan

Hiroshima Clinical Site2

🇯🇵

Hiroshima, Japan

Okayama Clinical Site

🇯🇵

Okayama, Japan

Tokushima Clinical Site

🇯🇵

Tokushima, Japan

Gyeonggi-do Clinical Site

🇰🇷

Suwon, Gyeonggi-do, Korea, Republic of

Gyeongsangnam-do Clinical Site

🇰🇷

Jinju-si, Gyeongsangnam-do, 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 Site6

🇰🇷

Seoul, Korea, Republic of

Chiayi Clinical Site

🇨🇳

Chiayi City, Taiwan

Kaohsiung Clinical Site2

🇨🇳

Kaohsiung, Taiwan

Taichung Clinical Site

🇨🇳

Taichung, Taiwan

Taipei Clinical Site2

🇨🇳

Taipei, Taiwan

Kanagawa Clinical Site2

🇯🇵

Yokohama, Kanagawa, Japan

Osaka Clinical Site

🇯🇵

Osaka, Japan

Tottori Clinical Site

🇯🇵

Yonago, Tottori, Japan

Ishikawa Clinical Site2

🇯🇵

Kanazawa, Ishikawa, Japan

Saitama Clinical Site

🇯🇵

Kitaadachi-gun, Saitama, Japan

Fukuoka Clinical Site4

🇯🇵

Fukuoka, Japan

Chiba Clinical Site

🇯🇵

Chiba, Japan

Fukushima Clinical Site

🇯🇵

Kōriyama, Fukushima, Japan

Iwate Clinical Site

🇯🇵

Morioka, Iwate, Japan

Kumamoto Clinical Site

🇯🇵

Kumamoto, Japan

Ehime Clinical Site

🇯🇵

Matsuyama, Ehime, Japan

Ibaraki Clinical Site

🇯🇵

Tsuchiura, Ibaraki, Japan

Kyoto Clinical Site

🇯🇵

Kyoto, Japan

Miyagi Clinical Site

🇯🇵

Sendai, Miyagi, Japan

Yamaguchi Clinical Site

🇯🇵

Yamaguchi, Japan

Chiba Clinical Site2

🇯🇵

Chiba, Japan

Gifu Clinical Site2

🇯🇵

Gifu, Japan

Gifu Clinical Site

🇯🇵

Gifu, Japan

Changhua Clinical Site

🇨🇳

Changhua, Taiwan

Tokyo Clinical Site2

🇯🇵

Shinjuku-Ku, Tokyo, Japan

Fukuoka Clinical Site

🇯🇵

Fukuoka, Japan

Hokkaido Clinical Site

🇯🇵

Sapporo, Hokkaido, Japan

Mie Clinical Site

🇯🇵

Tsu, Mie, Japan

Shimane Clinical Site

🇯🇵

Izumo, Shimane, Japan

Hiroshima Clinical Site

🇯🇵

Hiroshima, Japan

Taoyuan Clinical Site

🇨🇳

Taoyuan, Taiwan

Hyogo Clinical Site

🇯🇵

Takarazuka, Hyogo, Japan

Fukuoka Clinical Site2

🇯🇵

Fukuoka, Japan

Kochi Clinical Site

🇯🇵

Kochi, Japan

Okayama Clinical Site2

🇯🇵

Okayama, Japan

Toyama Clinical Site

🇯🇵

Toyama, Japan

Tainan Clinical Site

🇨🇳

Tainan, Taiwan

Tokyo Clinical Site3

🇯🇵

Shinjuku-Ku, Tokyo, Japan

Toyama Clinical Site2

🇯🇵

Toyama, Japan

Gangwon-Do Clinical Site

🇰🇷

Wŏnju, Gangwon-Do, Korea, Republic of

Aichi Clinical Site4

🇯🇵

Nagoya, Aichi, Japan

Oita Clinical Site

🇯🇵

Ōita, Japan

Nara Clinical Site

🇯🇵

Ikoma, Nara, Japan

Nagasaki Clinical Site

🇯🇵

Nagasaki, Japan

Tokyo Clinical Site

🇯🇵

Tachikawa, Tokyo, Japan

Fukui Clinical Site

🇯🇵

Fukui, Japan

Osaka Clinical Site3

🇯🇵

Osaka, Japan

Wakayama Clinical Site

🇯🇵

Wakayama, Japan

Gyeonggi-do Clinical Site2

🇰🇷

Seongnam-si, Gyeonggi-do, Korea, Republic of

Busan Clinical Site

🇰🇷

Busan, Korea, Republic of

Daegu Clinical Site

🇰🇷

Daegu, Korea, Republic of

Incheon Clinical Site

🇰🇷

Incheon, Korea, Republic of

Seoul Clinical Site5

🇰🇷

Seoul, Korea, Republic of

Seoul Clinical Site

🇰🇷

Seoul, Korea, Republic of

Kaohsiung Clinical Site

🇨🇳

Kaohsiung, Taiwan

Kaohsiung Clinical Site3

🇨🇳

Kaohsiung, Taiwan

Taipei Clinical Site

🇨🇳

Taipei, Taiwan

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