Carcinoma, Non-Small Cell Lung Cancer (NSCLC)
Conditions
Brief summary
The purpose of the study is to determine if nab-paclitaxel and carboplatin chemotherapy plus necitumumab is effective and safe in participants with stage IV squamous non-small cell lung cancer.
Interventions
Sponsors
Celgene
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
* Have histologically or cytologically confirmed squamous NSCLC. * Have stage IV disease at the time of study entry (American Joint Committee on Cancer \[AJCC\] Staging Manual, 7th edition). * Have measurable disease at the time of study enrollment as defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). * Have tumor tissue available for biomarker analysis. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Have adequate organ functions.
Exclusion criteria
* Are currently enrolled in another clinical trial. * Have received 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. * Have received previous chemotherapy for advanced NSCLC. Participants who have received adjuvant or neoadjuvant chemotherapy are eligible if the last administration of the prior regimens occurred at least 1 year prior to study entry. * Have undergone major surgery or received any investigational therapy in the 4 weeks prior to study entry. * Have undergone systemic radiotherapy within 4 weeks prior to study entry, or focal radiotherapy within 2 weeks prior to study entry. * Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). * Have a history of arterial or venous embolism within 6 months prior to study entry. * Have clinical evidence of concomitant infectious conditions. * Have a known allergy / history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of necitumumab, or any other contraindication to one of the administered treatments. * Are pregnant or breastfeeding. * Have a known history of drug abuse. * Have a concurrent active malignancy. Participants with a history of malignancy are eligible provided the participant has been disease-free for ≥3 years, with the following exception: Participants with adequately treated basal or squamous cell carcinoma of the skin, preinvasive carcinoma of the cervix, or any cancer that in the judgment of the investigator and Lilly clinical research physician/designee may not affect the interpretation of results (for example, prostate, bladder) are eligible. * Have discontinued investigational product or non approved use of a drug or device from a clinical trial within 30 days before the first day of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR]) | From Date of Randomization to Objective Disease Progression (Up to 18 Months) | ORR was the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of nontarget lesions, and no appearance of new lesions. Progressive disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From Date of Randomization until Death Due to Any Cause (Up to 18 Months) | OS defined as the time from the date of randomization to the date of death due to any cause. Participants who are alive at the time of study completion or are lost to follow-up will be censored at the time they were last known to be alive. |
| Percentage of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR]) | From Date of Randomization to Objective Disease Progression or Start of New Anticancer Therapy (Up to 18 Months) | Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and nontarget lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. |
| Progression Free Survival (PFS) | From Date of Randomization to Measured Progressive Disease or Death Due to Any Cause (Up to 18 Months) | PFS defined as time from date of randomization until first radiographic documentation of measured PD defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. PD was at least 20% increase in sum of diameters of target lesions with reference being smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.If participant does not have complete baseline disease assessment,PFS time censored at date of randomization,regardless of whether or not objectively determined disease progression or death observed for participant.If participant was not known to have died or have objective progression as of data inclusion cutoff date for analysis,the PFS time censored at last adequate tumor assessment date.The use of new anticancer therapy prior to occurrence of PD resulted in censoring at the date of last radiographic assessment prior to initiation of new therapy. |
| PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 1, 3 and 4: predose and <15minutes (min) post end-of-infusion | The Cmax is the maximum observed serum/plasma concentration of Necitumumab, Nab-Paclitaxel, and Carboplatin. |
| Immunogenicity: Number of Participants Developing Anti-drug Antibodies to Necitumumab | Predose Cycle 1 Through Short Term Follow Up (Up To 18 Months) | A participant was considered to have an anti-drug antibody response if anti-drug antibodies (ADA) were detected at any time point. |
| Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 3 and cycle 4: predose | The Cmin is the minimum observed serum/plasma concentration of Necitumumab, Nab-Paclitaxel, and Carboplatin. |
Countries
United States
Participant flow
Pre-assignment details
Participants with known best overall response and off study treatment were considered to be completed.
Participants by arm
| Arm | Count |
|---|---|
| Necitumumab + Nab-Paclitaxel + Carboplatin Induction: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles.
Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles).
Participants may continue to receive treatment until discontinuation criteria are met. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Induction Regimen | Death | 3 |
| Induction Regimen | On Study Treatment at Study Conclusion | 1 |
| Induction Regimen | Physician Decision | 1 |
| Induction Regimen | Withdrawal by Subject | 2 |
| Maintenance Regimen | Death | 1 |
| Maintenance Regimen | On Study Treatment at Study Conclusion | 1 |
Baseline characteristics
| Characteristic | Necitumumab + Nab-Paclitaxel + Carboplatin |
|---|---|
| Age, Continuous | 65.96 years STANDARD_DEVIATION 7.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 53 Participants |
| Region of Enrollment Germany | 4 Participants |
| Region of Enrollment Greece | 8 Participants |
| Region of Enrollment Spain | 27 Participants |
| Region of Enrollment United States | 15 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 54 | 1 / 34 |
| other Total, other adverse events | 54 / 54 | 31 / 34 |
| serious Total, serious adverse events | 18 / 54 | 5 / 34 |
Outcome results
Primary
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR])
ORR was the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of nontarget lesions, and no appearance of new lesions. Progressive disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time frame: From Date of Randomization to Objective Disease Progression (Up to 18 Months)
Population: All randomized participants who received at least 1 dose of study drug and who had a complete radiographic assessment at baseline and at least 1 complete radiographic assessment post-baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Necitumumab + Nab-Paclitaxel + Carboplatin | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR]) | 51.0 percentage of participants |
Secondary
Immunogenicity: Number of Participants Developing Anti-drug Antibodies to Necitumumab
A participant was considered to have an anti-drug antibody response if anti-drug antibodies (ADA) were detected at any time point.
Time frame: Predose Cycle 1 Through Short Term Follow Up (Up To 18 Months)
Population: All randomized participants who received at least 1 dose of study drug and had evaluable data for antibodies.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Necitumumab + Nab-Paclitaxel + Carboplatin | Immunogenicity: Number of Participants Developing Anti-drug Antibodies to Necitumumab | 3 Participants |
Secondary
Overall Survival (OS)
OS defined as the time from the date of randomization to the date of death due to any cause. Participants who are alive at the time of study completion or are lost to follow-up will be censored at the time they were last known to be alive.
Time frame: From Date of Randomization until Death Due to Any Cause (Up to 18 Months)
Population: All randomized participants who received at least 1 dose of study drug. Censored participants = 35.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Necitumumab + Nab-Paclitaxel + Carboplatin | Overall Survival (OS) | 15.54 Months |
Secondary
Percentage of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR])
Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and nontarget lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time frame: From Date of Randomization to Objective Disease Progression or Start of New Anticancer Therapy (Up to 18 Months)
Population: All randomized participants who received at least 1 dose of study drug and who had a complete radiographic assessment at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Necitumumab + Nab-Paclitaxel + Carboplatin | Percentage of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR]) | 78.4 percentage of participants |
Secondary
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin
The Cmin is the minimum observed serum/plasma concentration of Necitumumab, Nab-Paclitaxel, and Carboplatin.
Time frame: Cycle 3 and cycle 4: predose
Population: All randomized participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Necitumumab + Nab-Paclitaxel + Carboplatin | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 3 | 65.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 86.9 |
| Necitumumab + Nab-Paclitaxel + Carboplatin | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 4 | 90 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 74.9 |
| Carboplatin | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 3 | 0.131 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
| Carboplatin | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 4 | 0.209 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 197 |
| Paclitaxel | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 3 | 33.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 393 |
| Paclitaxel | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 4 | 107 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 313 |
Secondary
PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin
The Cmax is the maximum observed serum/plasma concentration of Necitumumab, Nab-Paclitaxel, and Carboplatin.
Time frame: Cycle 1, 3 and 4: predose and <15minutes (min) post end-of-infusion
Population: All randomized participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Necitumumab + Nab-Paclitaxel + Carboplatin | PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 3 | 291 ng/mL | Geometric Coefficient of Variation 46.5 |
| Necitumumab + Nab-Paclitaxel + Carboplatin | PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 1 | 231 ng/mL | Geometric Coefficient of Variation 27.1 |
| Necitumumab + Nab-Paclitaxel + Carboplatin | PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 4 | 277 ng/mL | Geometric Coefficient of Variation 42.5 |
| Carboplatin | PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 3 | 16 ng/mL | Geometric Coefficient of Variation 26.4 |
| Carboplatin | PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 1 | 16.4 ng/mL | Geometric Coefficient of Variation 22 |
| Carboplatin | PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 4 | 10.5 ng/mL | Geometric Coefficient of Variation 160 |
| Paclitaxel | PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 1 | 343 ng/mL | Geometric Coefficient of Variation 81.2 |
| Paclitaxel | PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 4 | 221 ng/mL | Geometric Coefficient of Variation 77.6 |
| Paclitaxel | PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin | Cycle 3 | 284 ng/mL | Geometric Coefficient of Variation 73 |
Secondary
Progression Free Survival (PFS)
PFS defined as time from date of randomization until first radiographic documentation of measured PD defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. PD was at least 20% increase in sum of diameters of target lesions with reference being smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.If participant does not have complete baseline disease assessment,PFS time censored at date of randomization,regardless of whether or not objectively determined disease progression or death observed for participant.If participant was not known to have died or have objective progression as of data inclusion cutoff date for analysis,the PFS time censored at last adequate tumor assessment date.The use of new anticancer therapy prior to occurrence of PD resulted in censoring at the date of last radiographic assessment prior to initiation of new therapy.
Time frame: From Date of Randomization to Measured Progressive Disease or Death Due to Any Cause (Up to 18 Months)
Population: All randomized participants who received at least 1 dose of study drug. Censored participants = 15.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Necitumumab + Nab-Paclitaxel + Carboplatin | Progression Free Survival (PFS) | 5.59 Months |