Advanced Non-small Cell Lung Cancer (NSCLC)
Conditions
Keywords
ONO-4538, Advanced non-small cell lung cancer (NSCLC), nivolumab
Brief summary
The objective of the study is to investigate the efficacy and safety of ONO-4538 in subjects with stage IIIB/IV or recurrent non-small cell lung cancer unsuited to radical radiotherapy and resistant to a platinum-based chemotherapeutic regimen.
Interventions
DRUGONO-4538
ONO-4538 Study in Patients With Squamous NSCLC
Sponsors
Ono Pharmaceutical Co. Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female ≥ 20 years of age 2. Histologically or cytologically confirmed non-small cell lung cancer 3. Diagnosis of NSCLC in stage IIIB/IV unsuited to radical radiotherapy according to UICC-TNM classification (7th edition) or recurrent NSCLC 4. Has at least one measurable lesion, as defined by the RECIST guideline (version 1.1)
Exclusion criteria
1. Current or prior severe hypersensitivity to another antibody product 2. Multiple primary cancers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Centrally Assessed) | Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or end of treatment phase (up to approximately 10 months).Follow-up phase: 28 days after final dose or for discontinuation occurring 28 or fewer days after final dose. | Response rate (%) = (Number of subjects whose confirmed best overall response was complete response (CR) or partial response (PR) / Total number of FAS)\*100. 95% Confidence interval (CI) was calculated by Wilson method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Investigator-assessed) | Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or end of treatment phase (up to approximately 10 months).Follow-up phase: 28 days after final dose or for discontinuation occurring 28 or fewer days after final dose. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Overall Survival | Follow-up phase: Every 6 months after the first day of treatment of the last subject enrolled in the study, until death or study completion. | Overall survival (days) = (the date of death due to any cause) - (the first dose date of investigational product) + 1. 95% CI was calculated by Kaplan-Meier method. |
| Progression Free Survival (Centrally Assessed) | Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or until central PD was confirmed or data cut-off point.Follow-up phase: Until beginning subsequent treatment for non-small cell lung cancer or PD or recurrence. | Progression free survival (days) = (the earlier date of the first documented progressive disease (PD) or death due to any cause) - (the first dose date of investigational product) + 1. 95% CI was calculated by Kaplan-Meier method. |
| Duration of Response (Centrally Assessed) | Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or end of treatment phase(up to approximately 10 months).Follow-up phase: Until beginning subsequent treatment for non-small cell lung cancer or PD or recurrence. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Duration of response (days) = (the date of the first documented PD or death due to any cause after response was confirmed) - (the date of the first confirmed CR or PR) + 1. Median (95% CI) was calculated by Kaplan-Meier method. |
Countries
South Korea
Participant flow
Pre-assignment details
Of 104 subjects determined eligible, 1 had an unknown histological type and excluded.
Participants by arm
| Arm | Count |
|---|---|
| Squamous Non-small Cell Lung Cancer (NSCLC) Refer to Participant Flow. | 44 |
| Non-squamous Non-small Cell Lung Cancer (NSCLC) Refer to Participant Flow. | 56 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 10 |
| Overall Study | Did not receive the investigational product | 1 | 2 |
| Overall Study | Disease progression | 20 | 27 |
| Overall Study | Met an exclusion criteria | 0 | 1 |
| Overall Study | Other than above reasons | 3 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 3 |
Baseline characteristics
| Characteristic | Squamous Non-small Cell Lung Cancer (NSCLC) | Total | Non-squamous Non-small Cell Lung Cancer (NSCLC) |
|---|---|---|---|
| Age, Continuous | 69.5 years | 66.5 years | 63.5 years |
| Age, Customized 65-<75 years | 21 Participants | 41 Participants | 20 Participants |
| Age, Customized <65 years | 14 Participants | 44 Participants | 30 Participants |
| Age, Customized >=75 years | 9 Participants | 15 Participants | 6 Participants |
| Brain metastasis No | 34 Participants | 74 Participants | 40 Participants |
| Brain metastasis Yes | 10 Participants | 26 Participants | 16 Participants |
| Disease stage IIIB | 5 Participants | 6 Participants | 1 Participants |
| Disease stage IV | 37 Participants | 91 Participants | 54 Participants |
| Disease stage Recurrent | 2 Participants | 3 Participants | 1 Participants |
| Eastern Cooperative Oncology Group performance status 0 | 6 Participants | 14 Participants | 8 Participants |
| Eastern Cooperative Oncology Group performance status 1 | 38 Participants | 86 Participants | 48 Participants |
| EGFR status Negative | 13 Participants | 56 Participants | 43 Participants |
| EGFR status Positive | 1 Participants | 8 Participants | 7 Participants |
| EGFR status Unknown | 30 Participants | 36 Participants | 6 Participants |
| Histology Adenocarcinoma | 0 Participants | 50 Participants | 50 Participants |
| Histology Large cell carcinoma | 0 Participants | 1 Participants | 1 Participants |
| Histology Other | 0 Participants | 5 Participants | 5 Participants |
| Histology Squamous | 44 Participants | 44 Participants | 0 Participants |
| Number of treatment regimens for NSCLC 1 | 42 Participants | 91 Participants | 49 Participants |
| Number of treatment regimens for NSCLC 2 | 2 Participants | 9 Participants | 7 Participants |
| Prior treatment for NSCLC-Medication: EGFR-TKI therapy No | 43 Participants | 92 Participants | 49 Participants |
| Prior treatment for NSCLC-Medication: EGFR-TKI therapy Yes | 1 Participants | 8 Participants | 7 Participants |
| Prior treatment for NSCLC-Medication: Platinum-based chemotherapy No | 0 Participants | 0 Participants | 0 Participants |
| Prior treatment for NSCLC-Medication: Platinum-based chemotherapy Yes | 44 Participants | 100 Participants | 56 Participants |
| Prior treatment for NSCLC: Radiotherapy No | 33 Participants | 76 Participants | 43 Participants |
| Prior treatment for NSCLC: Radiotherapy Yes | 11 Participants | 24 Participants | 13 Participants |
| Prior treatment for NSCLC: Surgery No | 35 Participants | 82 Participants | 47 Participants |
| Prior treatment for NSCLC: Surgery Yes | 9 Participants | 18 Participants | 9 Participants |
| Region of Enrollment South Korea | 44 Participants | 100 Participants | 56 Participants |
| Sex: Female, Male Female | 0 Participants | 22 Participants | 22 Participants |
| Sex: Female, Male Male | 44 Participants | 78 Participants | 34 Participants |
| Smoking history Current/former smoker | 43 Participants | 78 Participants | 35 Participants |
| Smoking history Never smoker | 1 Participants | 22 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 44 | 15 / 56 |
| other Total, other adverse events | 24 / 44 | 36 / 56 |
| serious Total, serious adverse events | 20 / 44 | 17 / 56 |
Outcome results
Primary
Response Rate (Centrally Assessed)
Response rate (%) = (Number of subjects whose confirmed best overall response was complete response (CR) or partial response (PR) / Total number of FAS)\*100. 95% Confidence interval (CI) was calculated by Wilson method.
Time frame: Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or end of treatment phase (up to approximately 10 months).Follow-up phase: 28 days after final dose or for discontinuation occurring 28 or fewer days after final dose.
Population: Full analysis set（FAS): This set was defined as a full group of subjects who were included in safety analysis set, which was defined as group of subjects who were enrolled and received at least one dose of the study drug. This set was used in the primary efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Squamous Non-small Cell Lung Cancer (NSCLC) | Response Rate (Centrally Assessed) | 13.6 percentage of participants |
| Non-squamous Non-small Cell Lung Cancer (NSCLC) | Response Rate (Centrally Assessed) | 19.6 percentage of participants |
Secondary
Duration of Response (Centrally Assessed)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Duration of response (days) = (the date of the first documented PD or death due to any cause after response was confirmed) - (the date of the first confirmed CR or PR) + 1. Median (95% CI) was calculated by Kaplan-Meier method.
Time frame: Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or end of treatment phase(up to approximately 10 months).Follow-up phase: Until beginning subsequent treatment for non-small cell lung cancer or PD or recurrence.
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Squamous Non-small Cell Lung Cancer (NSCLC) | Duration of Response (Centrally Assessed) | NA days |
| Non-squamous Non-small Cell Lung Cancer (NSCLC) | Duration of Response (Centrally Assessed) | NA days |
Secondary
Overall Survival
Overall survival (days) = (the date of death due to any cause) - (the first dose date of investigational product) + 1. 95% CI was calculated by Kaplan-Meier method.
Time frame: Follow-up phase: Every 6 months after the first day of treatment of the last subject enrolled in the study, until death or study completion.
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Squamous Non-small Cell Lung Cancer (NSCLC) | Overall Survival | NA days |
| Non-squamous Non-small Cell Lung Cancer (NSCLC) | Overall Survival | NA days |
Secondary
Progression Free Survival (Centrally Assessed)
Progression free survival (days) = (the earlier date of the first documented progressive disease (PD) or death due to any cause) - (the first dose date of investigational product) + 1. 95% CI was calculated by Kaplan-Meier method.
Time frame: Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or until central PD was confirmed or data cut-off point.Follow-up phase: Until beginning subsequent treatment for non-small cell lung cancer or PD or recurrence.
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Squamous Non-small Cell Lung Cancer (NSCLC) | Progression Free Survival (Centrally Assessed) | 67.0 days |
| Non-squamous Non-small Cell Lung Cancer (NSCLC) | Progression Free Survival (Centrally Assessed) | 162.0 days |
Secondary
Response Rate (Investigator-assessed)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or end of treatment phase (up to approximately 10 months).Follow-up phase: 28 days after final dose or for discontinuation occurring 28 or fewer days after final dose.
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Squamous Non-small Cell Lung Cancer (NSCLC) | Response Rate (Investigator-assessed) | 18.2 percentage of participants |
| Non-squamous Non-small Cell Lung Cancer (NSCLC) | Response Rate (Investigator-assessed) | 19.6 percentage of participants |