Malignant Solid Tumor
Conditions
Keywords
Advanced Malignant Solid Tumors, Solid Cancers, Non-small Cell Lung Cancer, NSCLC, Breast Cancer
Brief summary
The purpose of this study is to investigate the pharmacokinetics (PK) of necitumumab in combination with gemcitabine-cisplatin in participants with advanced malignant solid tumors and to assess the potential for drug-drug interactions between necitumumab and gemcitabine-cisplatin.
Interventions
BIOLOGICALNecitumumab
PK Run-In Period: Necitumumab administered on Day 3 of the 3-week PK run-in period as an intravenous (I.V.) infusion at an absolute dose of 800 mg Treatment Cycles: Necitumumab administered on Days 1 and 8 of every 3-week cycle as an intravenous (I.V.) infusion at an absolute dose of 800 mg Participants in Cohort 1 will receive necitumumab Process C drug product and participants in Cohort 2 will receive necitumumab Process D drug product
DRUGGemcitabine
PK Run-In Period: Gemcitabine administered on Day 1 of the 3-week PK run-in period as an I.V. infusion at a dose of 1250 milligram per square meter (mg/m2) Treatment Cycles: Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an I.V. infusion at a dose of 1250 mg/m2
DRUGCisplatin
PK Run-In Period: Cisplatin administered on Day 1 of the 3-week PK run-in period as an I.V. infusion at a dose of 75 mg/m2 Treatment Cycles: Cisplatin administered on Day 1 of every 3-week cycle as an I.V. infusion at a dose of 75 mg/m2
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
* Have documented advanced or metastatic malignant solid tumors (except for colorectal tumors with KRAS mutation) that are resistant to standard therapy or for which no standard therapy is available * May have measurable or non-measurable disease * Have resolution to Grade 0 or 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE 4.0) of all clinically significant toxic effects (other than alopecia) of prior chemotherapy, surgery, radiotherapy, or hormonal therapy * Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1 * Have adequate hepatic, hematologic and renal function * If female, are surgically sterile, postmenopausal, or agree to be compliant with a highly effective contraceptive method during and for 6 months after the treatment period. If male, are surgically sterile or agree to be compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period * Female participants of childbearing potential have a negative serum pregnancy test within 7 days prior to the first dose of study therapy
Exclusion criteria
* Have received a systemic anticancer agent (including EGFR tyrosine kinase inhibitors) or device within 28 days prior to first dose of study therapy * The most recent anticancer therapy received by the participant included either gemcitabine or cisplatin (or both) * Have received radiotherapy within 14 days prior to first dose of study therapy * Have received cytotoxic chemotherapy within 21 days prior to first dose of study therapy * Are receiving concurrent treatment with another anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiation therapy, chemoembolization, or targeted therapy * Are considered surgical candidates (with resectable disease) * Have brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants * Have narrowing of or blockage in large veins * Have coronary artery disease or uncontrolled congestive heart failure * Have uncontrolled angina pectoris, or experienced myocardial infarction within 6 months prior to first dose of study therapy * Have an ongoing or active infection (requiring treatment), including active tuberculosis or known infection with the human immunodeficiency virus * Have a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder * Have known drug or alcohol abuse * If female, are pregnant or breastfeeding * Have had major surgery within 28 days prior to first dose of study medication or subcutaneous venous access device implantation within 7 days prior to first dose of study therapy * Are currently enrolled in, or discontinued within the 30 days prior to first dose of study therapy from a clinical trial involving an investigational product or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PK: Dose Normalized AUC(0-∞) of Gemcitabine | Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion |
| PK: Area Under Concentration-Time Curve From Zero to Time 168 (AUC[-168]) of Necitumumab | Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion |
| PK: Dose-Normalized AUC(0-24) of Gemcitabine | Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion |
| PK: Dose-Normalized AUC(0-5) of Cisplatin | Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion |
| PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, (AUC[0-∞]) of Necitumumab | Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1 Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion |
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab | Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 Hour (h) Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion |
| PK: Dose-Normalized Cmax of Gemcitabine | Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion |
| PK: Dose-Normalized Cmax of Cisplatin | Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) (Antitumor Activity of Necitumumab in Combination With Gemcitabine-cisplatin Chemotherapy) | Baseline to Measured Progressive Disease (Up to 14 Months) | ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, CR was defined as the disappearance of all target and non-target lesions; 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. Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) \* 100. |
| PK: Cmax of Necitumumab After Administration of Process C and Process D Drug Product | Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion | — |
| PK: AUC(0-∞) of Necitumumab After Administration of Process C and Process D Drug Product | Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion | — |
| Number of Participants With Anti-Necitumumab Antibodies | Baseline through, 30-Day Follow-Up | A participant was considered to have an anti-necitumumab antibody response if anti-drug antibodies (ADA) were confirmed positive. Treatment emergent antibodies were defined as any anti-necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer. |
Countries
United States
Participant flow
Pre-assignment details
Cohort 1 'completers' completed the PK run-in period (3 Weeks) and Cycle 1, Day 1 and Cohort 2 'completers' completed the PK run-in period.
Participants by arm
| Arm | Count |
|---|---|
| Necitumumab Cohort 1 Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg.
Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product.
Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2.
Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. | 18 |
| Necitumumab Cohort 2 Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg.
Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product.
Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2.
Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2. | 17 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Progressive Disease | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Necitumumab Cohort 2 | Necitumumab Cohort 1 | Total |
|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 13.84 | 55.3 years STANDARD_DEVIATION 15.54 | 56.7 years STANDARD_DEVIATION 14.59 |
| Disease Characteristics - Tumor Type Adenocarcinoma of the Ampula of Vater | 1 participants | 0 participants | 1 participants |
| Disease Characteristics - Tumor Type Breast Carcinoma | 4 participants | 3 participants | 7 participants |
| Disease Characteristics - Tumor Type Colorectal Carcinoma | 1 participants | 0 participants | 1 participants |
| Disease Characteristics - Tumor Type Endometrial Carcinoma | 1 participants | 1 participants | 2 participants |
| Disease Characteristics - Tumor Type Esophageal Carcinoma | 1 participants | 0 participants | 1 participants |
| Disease Characteristics - Tumor Type Granulosa Cell Tumor of the Ovary | 0 participants | 1 participants | 1 participants |
| Disease Characteristics - Tumor Type Head and Neck Carcinoma | 1 participants | 1 participants | 2 participants |
| Disease Characteristics - Tumor Type Hepatobilliary Carcinoma | 0 participants | 1 participants | 1 participants |
| Disease Characteristics - Tumor Type Hepatocellular Carcinoma | 1 participants | 0 participants | 1 participants |
| Disease Characteristics - Tumor Type Left Parotid | 0 participants | 1 participants | 1 participants |
| Disease Characteristics - Tumor Type Liver | 0 participants | 1 participants | 1 participants |
| Disease Characteristics - Tumor Type Melanoma | 1 participants | 1 participants | 2 participants |
| Disease Characteristics - Tumor Type Mesothelioma | 1 participants | 0 participants | 1 participants |
| Disease Characteristics - Tumor Type Neuroendocrine Tumor | 1 participants | 0 participants | 1 participants |
| Disease Characteristics - Tumor Type Nonsmall Cell Lung Carcinoma | 0 participants | 2 participants | 2 participants |
| Disease Characteristics - Tumor Type Ovarian Carcinoma | 1 participants | 2 participants | 3 participants |
| Disease Characteristics - Tumor Type Pancreatic Carcinoma | 1 participants | 0 participants | 1 participants |
| Disease Characteristics - Tumor Type Sarcoma, soft tissue | 1 participants | 0 participants | 1 participants |
| Disease Characteristics - Tumor Type Small Cell Lung Carcinoma | 1 participants | 2 participants | 3 participants |
| Disease Characteristics - Tumor Type Thymic Tumor | 0 participants | 2 participants | 2 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline 0 | 7 participants | 9 participants | 16 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline 1 | 10 participants | 9 participants | 19 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline >=2 | 0 participants | 0 participants | 0 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 17 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Prior Anti-Cancer Therapy Any Prior (Adjuvant/Neoadjuvant) Systemic Therapy | 16 participants | 17 participants | 33 participants |
| Prior Anti-Cancer Therapy Any Prior Radiotherapy | 10 participants | 13 participants | 23 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 17 Participants | 31 Participants |
| Region of Enrollment United States | 17 participants | 18 participants | 35 participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 18 | 17 / 17 |
| serious Total, serious adverse events | 5 / 18 | 8 / 17 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab
Time frame: Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 Hour (h) Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion
Population: All participants who received at least one dose of study drug and had evaluable data for PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab | 277 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 22 |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab | 315 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 23 |
Primary
PK: Area Under Concentration-Time Curve From Zero to Time 168 (AUC[-168]) of Necitumumab
Time frame: Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion
Population: All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | PK: Area Under Concentration-Time Curve From Zero to Time 168 (AUC[-168]) of Necitumumab | 21900 ug*hour(h)/mL | Geometric Coefficient of Variation 24 |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | PK: Area Under Concentration-Time Curve From Zero to Time 168 (AUC[-168]) of Necitumumab | 22900 ug*hour(h)/mL | Geometric Coefficient of Variation 34 |
Primary
PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, (AUC[0-∞]) of Necitumumab
Time frame: Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1 Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion
Population: All participants who received at least one dose of study drug and had evaluable data for PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, (AUC[0-∞]) of Necitumumab | 33800 ug*h/mL | Geometric Coefficient of Variation 33 |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, (AUC[0-∞]) of Necitumumab | 26400 ug*h/mL | Geometric Coefficient of Variation 30 |
Primary
PK: Dose-Normalized AUC(0-24) of Gemcitabine
Time frame: Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion
Population: All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | PK: Dose-Normalized AUC(0-24) of Gemcitabine | 2.71 ng*h/mL/mg | Geometric Coefficient of Variation 45 |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | PK: Dose-Normalized AUC(0-24) of Gemcitabine | 3.31 ng*h/mL/mg | Geometric Coefficient of Variation 33 |
Primary
PK: Dose-Normalized AUC(0-5) of Cisplatin
Time frame: Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion
Population: All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | PK: Dose-Normalized AUC(0-5) of Cisplatin | 61.5 ng*h/mL/mg | Geometric Coefficient of Variation 20 |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | PK: Dose-Normalized AUC(0-5) of Cisplatin | 67.3 ng*h/mL/mg | Geometric Coefficient of Variation 24 |
Primary
PK: Dose Normalized AUC(0-∞) of Gemcitabine
Time frame: Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion
Population: All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | PK: Dose Normalized AUC(0-∞) of Gemcitabine | 2.72 ng*h/mL/mg | Geometric Coefficient of Variation 45 |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | PK: Dose Normalized AUC(0-∞) of Gemcitabine | 3.32 ng*h/mL/mg | Geometric Coefficient of Variation 33 |
Primary
PK: Dose-Normalized Cmax of Cisplatin
Time frame: Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion
Population: All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | PK: Dose-Normalized Cmax of Cisplatin | 19.2 nanogram (ng)/mL/mg | Geometric Coefficient of Variation 21 |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | PK: Dose-Normalized Cmax of Cisplatin | 22.1 nanogram (ng)/mL/mg | Geometric Coefficient of Variation 30 |
Primary
PK: Dose-Normalized Cmax of Gemcitabine
Time frame: Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion
Population: All participants who received at least one dose of study drug and had evaluable data for PK. Per protocol, no data were collected for this assessment for participants in Cohort 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | PK: Dose-Normalized Cmax of Gemcitabine | 4.83 nanogram(ng)/mL/mg | Geometric Coefficient of Variation 66 |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | PK: Dose-Normalized Cmax of Gemcitabine | 7.87 nanogram(ng)/mL/mg | Geometric Coefficient of Variation 43 |
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 confirmed positive. 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 through, 30-Day Follow-Up
Population: All participants who received at least one dose of study drug and had evaluable baseline and postbaseline data for antibodies.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | Number of Participants With Anti-Necitumumab Antibodies | ADA Positive | 3 participants with immunogenicity samples |
| Necitumumab Cohort 1 Day 3 Run-in | Number of Participants With Anti-Necitumumab Antibodies | TE Antibodies | 1 participants with immunogenicity samples |
| Necitumumab Cohort 1 Day 3 Run-in | Number of Participants With Anti-Necitumumab Antibodies | Neutralizing Antibodies | 0 participants with immunogenicity samples |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | Number of Participants With Anti-Necitumumab Antibodies | ADA Positive | 0 participants with immunogenicity samples |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | Number of Participants With Anti-Necitumumab Antibodies | TE Antibodies | 0 participants with immunogenicity samples |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | Number of Participants With Anti-Necitumumab Antibodies | Neutralizing Antibodies | 0 participants with immunogenicity samples |
Secondary
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) (Antitumor Activity of Necitumumab in Combination With Gemcitabine-cisplatin Chemotherapy)
ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, CR was defined as the disappearance of all target and non-target lesions; 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. Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) \* 100.
Time frame: Baseline to Measured Progressive Disease (Up to 14 Months)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) (Antitumor Activity of Necitumumab in Combination With Gemcitabine-cisplatin Chemotherapy) | 16.7 percentage of participants |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) (Antitumor Activity of Necitumumab in Combination With Gemcitabine-cisplatin Chemotherapy) | 5.9 percentage of participants |
Secondary
PK: AUC(0-∞) of Necitumumab After Administration of Process C and Process D Drug Product
Time frame: Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion
Population: All participants who received at least one dose of study drug and had evaluable data for PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | PK: AUC(0-∞) of Necitumumab After Administration of Process C and Process D Drug Product | 33800 ug*h/mL | Geometric Coefficient of Variation 33 |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | PK: AUC(0-∞) of Necitumumab After Administration of Process C and Process D Drug Product | 35500 ug*h/mL | Geometric Coefficient of Variation 35 |
Secondary
PK: Cmax of Necitumumab After Administration of Process C and Process D Drug Product
Time frame: Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion
Population: All participants who received at least one dose of study drug and had evaluable data for PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Necitumumab Cohort 1 Day 3 Run-in | PK: Cmax of Necitumumab After Administration of Process C and Process D Drug Product | 277 ug/mL | Geometric Coefficient of Variation 22 |
| Necitumumab Cohort 1 Day 1, Cycle 1, Combination | PK: Cmax of Necitumumab After Administration of Process C and Process D Drug Product | 300 ug/mL | Geometric Coefficient of Variation 36 |