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

Study Overview
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Brief Summary
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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.

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

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: ONO-4538
* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: Bevacizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ONO-4538 group<br>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<br>* 360 mg solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.<br>Drug: Carboplatin<br>* 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.<br>Drug: Paclitaxel<br>* 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.<br>Drug: Bevacizumab<br>* Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.<br>|
| Placebo Comparator: Placebo group<br>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<br>* 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.<br>Drug: Paclitaxel<br>* 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.<br>Drug: Bevacizumab<br>* Bevacizumab at 15 mg/kg intravenously in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.<br>Drug: Placebo<br>* Placebo solution intravenously for 30 min in every 3 weeks until RECIST 1.1 defined PD, unacceptable toxicity, or withdrawal of consent.<br>|

What is the study measuring?
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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 |