Non-small Cell Lung Cancer
Conditions
Brief summary
The purpose of this study is to see how participants with late stage lung cancer do on gemcitabine-cisplatin chemotherapy plus necitumumab. The study will also see how safe the drugs are in combination and to see how long the medicine stays in the body. The study will last approximately 2 years.
Interventions
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed squamous Non-small Cell Lung Cancer (NSCLC) * Stage IV disease at time of study entry based on American Joint Committee on Cancer 7th edition * Measurable disease at time of study entry as defined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 * Required to have a performance status (PS) 0-1
Exclusion criteria
* Nonsquamous NSCLC * Prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), or VEGF receptor * Previous chemotherapy for NSCLC * Major surgery or received any investigational therapy in the 4 weeks prior to study enrollment * Chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed) * Brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants (participants who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) Objective Tumor Response Rate (ORR) | Baseline to Measured Progressive Disease (up to 17 Months) | ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, PR defined as a \>30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: total number of participants with a best tumor response of PR or CR among participants counted in the denominator/total number of participants treated with any amount of study drug, who has a complete radiographic assessment at baseline, and who has at least 1 complete radiographic assessment at postbaseline x 100%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Baseline to Measured Progressive Disease or Death from Any Cause (up to 17 Months) | PFS is defined as the time from the date of first dose of study drug until objective progressive disease (PD) or death for any cause. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions was also considered progression. For participants not known to have died as of the data cut-off date and who do not have objective PD, PFS will be censored at the date of the last complete radiographic assessment. |
| Number of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Disease Control Rate (DCR)] | Baseline to Measured Progressive Disease or Participants Stops Study (up to 17 Months) | DCR is best overall response of SD, PR or CR. According to RECIST v1.1, PR defined as a ≥30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. Percentage of participants who achieved disease control = (those participants counted in the denominator with a best tumor response of SD, PR, or CR)/(the same denominator as for ORR)\*100. |
| Overall Survival (OS) | Baseline to Death from Any Cause (up to 17 Months) | Overall survival (OS) duration is defined from the date of first dose of study drug to the date of death from any cause. OS was estimated by the Kaplan-Meier method. For participants who were not known to have died as of the data cut-off date, OS was censored at the date of last contact prior to the data cutoff date. |
| Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab | Predose Cycle 1 Day 8; Cycle 2 through 6 Day 1; End of Infusion (EOI) Cycle 1, 3, 5 Day 1 | Pre-infusion Minimum Concentration (Cmin) and post-infusion (Cmax) necitumumab serum concentration |
| Number of Participants With Anti-Necitumumab Antibodies | Baseline up to 30 Days Post Last Infusion (up to 17 Months) | A participant was considered to have an anti-necitumumab antibody response if anti-drug antibodies (ADA) were detected at any time point. Treatment emergent antibodies were defined as any anti-necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer. |
| Percent Change in Tumor Size (CTS) | Baseline until Measured Progressive Disease (up to 17 Months) | CTS is defined as maximum percent improvement from baseline in the sum of target lesions. |
Countries
Canada, France, Mexico, Netherlands, Spain, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine + Cisplatin + Necitumumab Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle.
Gemcitabine administered IV at 1250 milligram per square meter (mg/m\^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles.
Cisplatin administered IV at 75 mg/m\^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles. | 61 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Clinical Progressive Disease | 3 |
| Overall Study | Death | 4 |
Baseline characteristics
| Characteristic | Gemcitabine + Cisplatin + Necitumumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 33 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Race/Ethnicity, Customized Asian | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants |
| Race/Ethnicity, Customized White | 48 Participants |
| Region of Enrollment Canada | 5 participants |
| Region of Enrollment France | 3 participants |
| Region of Enrollment Korea, Republic of | 3 participants |
| Region of Enrollment Mexico | 1 participants |
| Region of Enrollment Netherlands | 5 participants |
| Region of Enrollment Spain | 25 participants |
| Region of Enrollment Taiwan | 8 participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 61 / 61 |
| serious Total, serious adverse events | 33 / 61 |
Outcome results
Primary
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) Objective Tumor Response Rate (ORR)
ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, PR defined as a \>30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: total number of participants with a best tumor response of PR or CR among participants counted in the denominator/total number of participants treated with any amount of study drug, who has a complete radiographic assessment at baseline, and who has at least 1 complete radiographic assessment at postbaseline x 100%.
Time frame: Baseline to Measured Progressive Disease (up to 17 Months)
Population: All participants who received any amount of study treatment and had evaluable baseline and postbaseline data for radiographic assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine + Cisplatin + Necitumumab | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) Objective Tumor Response Rate (ORR) | 48.1 Percentage of participants |
Secondary
Number of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Disease Control Rate (DCR)]
DCR is best overall response of SD, PR or CR. According to RECIST v1.1, PR defined as a ≥30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. Percentage of participants who achieved disease control = (those participants counted in the denominator with a best tumor response of SD, PR, or CR)/(the same denominator as for ORR)\*100.
Time frame: Baseline to Measured Progressive Disease or Participants Stops Study (up to 17 Months)
Population: All participants who received any quantity of study treatment and had evaluable baseline and postbaseline data for radiographic assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine + Cisplatin + Necitumumab | Number of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Disease Control Rate (DCR)] | 81.5 percentage of participants |
Secondary
Number of Participants With Anti-Necitumumab Antibodies
A participant was considered to have an anti-necitumumab antibody response if anti-drug antibodies (ADA) were detected at any time point. Treatment emergent antibodies were defined as any anti-necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer.
Time frame: Baseline up to 30 Days Post Last Infusion (up to 17 Months)
Population: All participants who received any amount of study treatment and had evaluable baseline and postbaseline data for antibodies.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine + Cisplatin + Necitumumab | Number of Participants With Anti-Necitumumab Antibodies | Number of Participants with 1 Positive Titer | 9 participants |
| Gemcitabine + Cisplatin + Necitumumab | Number of Participants With Anti-Necitumumab Antibodies | Treatment Emergent Antibody Positive | 4 participants |
| Gemcitabine + Cisplatin + Necitumumab | Number of Participants With Anti-Necitumumab Antibodies | Neutralizing Antibody Detected | 3 participants |
Secondary
Overall Survival (OS)
Overall survival (OS) duration is defined from the date of first dose of study drug to the date of death from any cause. OS was estimated by the Kaplan-Meier method. For participants who were not known to have died as of the data cut-off date, OS was censored at the date of last contact prior to the data cutoff date.
Time frame: Baseline to Death from Any Cause (up to 17 Months)
Population: All participants who received any amount of study treatment. Participants censored=34.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine + Cisplatin + Necitumumab | Overall Survival (OS) | 11.7 months |
Secondary
Percent Change in Tumor Size (CTS)
CTS is defined as maximum percent improvement from baseline in the sum of target lesions.
Time frame: Baseline until Measured Progressive Disease (up to 17 Months)
Population: All participants who received any quantity of study treatment and had evaluable baseline and postbaseline data for CTS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gemcitabine + Cisplatin + Necitumumab | Percent Change in Tumor Size (CTS) | 39.68 percent change | Standard Deviation 21.296 |
Secondary
Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab
Pre-infusion Minimum Concentration (Cmin) and post-infusion (Cmax) necitumumab serum concentration
Time frame: Predose Cycle 1 Day 8; Cycle 2 through 6 Day 1; End of Infusion (EOI) Cycle 1, 3, 5 Day 1
Population: All participants who received any amount of study treatment and had evaluable data for Cmax
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcitabine + Cisplatin + Necitumumab | Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab | Predose Cycle 6 Day 1 | 126 micrograms/milliliter (ug/ml) | Geometric Coefficient of Variation 34.2 |
| Gemcitabine + Cisplatin + Necitumumab | Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab | Predose Cycle 1 Day 8 | 70.8 micrograms/milliliter (ug/ml) | Geometric Coefficient of Variation 36.7 |
| Gemcitabine + Cisplatin + Necitumumab | Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab | Predose Cycle 2 Day 1 | 67.5 micrograms/milliliter (ug/ml) | Geometric Coefficient of Variation 78 |
| Gemcitabine + Cisplatin + Necitumumab | Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab | Predose Cycle 3 Day 1 | 106 micrograms/milliliter (ug/ml) | Geometric Coefficient of Variation 36.6 |
| Gemcitabine + Cisplatin + Necitumumab | Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab | Predose Cycle 4 Day 1 | 115 micrograms/milliliter (ug/ml) | Geometric Coefficient of Variation 43.9 |
| Gemcitabine + Cisplatin + Necitumumab | Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab | Predose Cycle 5 Day 1 | 141 micrograms/milliliter (ug/ml) | Geometric Coefficient of Variation 62.3 |
| Gemcitabine + Cisplatin + Necitumumab | Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab | EOI Cycle 1 Day 1 | 266 micrograms/milliliter (ug/ml) | Geometric Coefficient of Variation 24.8 |
| Gemcitabine + Cisplatin + Necitumumab | Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab | EOI Cycle 3 Day 1 | 352 micrograms/milliliter (ug/ml) | Geometric Coefficient of Variation 29.5 |
| Gemcitabine + Cisplatin + Necitumumab | Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab | EOI Cycle 5 Day 1 | 360 micrograms/milliliter (ug/ml) | Geometric Coefficient of Variation 29.2 |
Secondary
Progression Free Survival (PFS)
PFS is defined as the time from the date of first dose of study drug until objective progressive disease (PD) or death for any cause. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions was also considered progression. For participants not known to have died as of the data cut-off date and who do not have objective PD, PFS will be censored at the date of the last complete radiographic assessment.
Time frame: Baseline to Measured Progressive Disease or Death from Any Cause (up to 17 Months)
Population: All participants who received any quantity of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine + Cisplatin + Necitumumab | Progression Free Survival (PFS) | 5.6 months |