Stage IV Non-Small Cell Lung Cancer
Conditions
Brief summary
The main purpose of this study is to evaluate the safety and efficacy of the combination of necitumumab with pembrolizumab in participants with stage IV non-small cell lung cancer (NSCLC).
Interventions
DRUGNecitumumab
Administered IV
DRUGPembrolizumab
Administered IV
Sponsors
Merck Sharp & Dohme LLC
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The participant has Stage IV NSCLC. * Part A: NSCLC Stage IV (any type) * Part B: NSCLC Stage IV (squamous and nonsquamous) * Part C: NSCLC Stage IV in Japanese participants (squamous and nonsquamous) * The participant must have progressed after 1 platinum-based chemotherapy regimen for Stage IV NSCLC. Prior therapy with VEGF/VEGFR targeting agents is permitted. Prior neoadjuvant/adjuvant therapy is permitted. Prior treatment with EGFR-TKI and ALK inhibitors is mandatory in participants with NSCLC whose tumor has EGFR-activating mutations or ALK translocations, respectively. * Measurable disease at the time of study entry as defined by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). * The participant has evaluable tumor tissue available for biomarker analyses. * The participant has adequate organ function. * Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-1.
Exclusion criteria
* The participant is currently enrolled in a clinical trial involving an investigational product or non-approved use of a drug or device. * Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 monoclonal antibody. * Have a serious concomitant systemic disorder or significant cardiac disease. * The participant has undergone major surgery or received anti-cancer monoclonal antibody therapy in the 30-days prior to study enrollment. * The participant has undergone chest irradiation within 2 weeks prior to receiving study treatment. * The participant has brain metastases that are symptomatic. * The participant has a history of arterial thromboembolism event (ATE) or venous thromboembolism event (VTE) within 3 months prior to study enrollment. Participants with history of VTE beyond 3 months prior to study enrollment can be enrolled if they are appropriately treated with low molecular weight heparin. * The participant has a known allergy / history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of necitumumab or pembrolizumab, or any other contraindication to one of the administered treatments. * The participant has a concurrent active malignancy. Previous history of malignancy is permitted, provided that the participant has been free of disease for ≥3 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin, preinvasive carcinoma of the cervix, or any cancers that in the judgment of the investigator and sponsor may not affect the interpretation of results (for example, prostate, bladder). * History of interstitial lung disease, pneumonitis, autoimmune disease or syndrome that requires steroids or immunosuppressive agents. * The participant has active infection requiring systemic therapy, including active tuberculosis or known history of infection with the human immunodeficiency virus (HIV 1/2 antibodies), or hepatitis B (e.g., HBsAg reactive) and/or C virus (e.g., HCV RNA \[qualitative\] is detected). * The participant has an active autoimmune disease or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. * The participant has received a live vaccine within 30 days prior to the first dose of trial treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) in Part A and Part C | Baseline through Cycle 1 (21 day cycles) | A dose limiting toxicity (DLT) was defined as an adverse event (AE) during the first 21 days that was possibly related to the study drug and fulfilled any of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0: Grade 3 or 4 nonhematologic toxicity, Grade 4 nausea, vomiting, or diarrhea that persists more than 3 days despite maximal supportive intervention, Grade 3 thrombocytopenia with bleeding requiring transfusion, Grade 4 thrombocytopenia with or without bleeding, Grade 4 neutropenia that persists more than 5 days, Grade 3 or 4 neutropenia with fever, Grade ≥3 skin toxicity despite best supportive care with some exceptions, if a total at least 75% of the planned dose for both agents cannot be administered in the first cycle due to toxicity, prolonged delay (\>2 weeks) in initiating cycle 2 due to treatment-related toxicity and Grade 5 toxicity. |
| Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) in Part A and Part B | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 16 Months) | ORR was the percentage of participants achieving a best overall response (BOR) 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 non-target lesions, and no appearance of new lesions. Progressive disease (PD) is defined as 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 |
|---|---|---|
| Number of Participants With Anti-Necitumumab Antibodies in Part A, Part B and Part C | Predose Cycle 1 Day 1 through Predose Cycle 8 Day 1 (21 Day Cycles) | Result is considered as treatment emergent anti-necitumumab antibody positive if postbaseline titer = 4\*baseline titer for baseline titer \> 0 or if postbaseline titer \>= 20 for samples with antibody not detected. |
| Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR]) in Part A Cohort 2 and Part B | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 16 Months) | Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by 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 non-target lesions, and no appearance of new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. PD is defined as 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. |
| Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) in Part A Cohort 2, Part B and Part C | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 40 Months) | ORR was the percentage of participants achieving a best overall response (BOR) 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 non-target lesions, and no appearance of new lesions. PD is defined as 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) in Part A Cohort 2 and Part B | Baseline to Measured Progressive Disease or Death Due to Any Cause (Up To 16 Months) | PFS was defined as the time from the date of first dose of study drug until first observation of objective (radiographically documented) PD as defined by RECIST v1.1 or death from any cause, whichever comes first. PD is defined as 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. |
| Overall Survival (OS) in Part A Cohort 2, Part B | Baseline to Death from Any Cause (Up To 16 Months) | OS duration was measured from the date of first dose of study drug (necitumumab and/or pembrolizumab) to the date of death from any cause. |
| Duration of Response (DoR) in Part A Cohort 2 and Part B | Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up To 16 Months) | DOR was defined only for responders (participants with confirmed CR or PR). It was measured from the date of first evidence of a confirmed CR or PR to the date of objective progression or the date of death due to any cause, whichever was earlier. |
| Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Predose sample (within 1 hour before infusion) and postdose sample (within 10 min after infusion) on Day 1 at Cycles 1, 2, 4, 6, 8; 30 days post treatment discontinuation | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab. |
Countries
France, Japan, Spain, United States
Participant flow
Pre-assignment details
Per protocol, participants in Part A Cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab (pembro) absolute dose by intravenous (IV) infusion on Day1 of 21 days cycles followed by 600 mg necitumumab (Neci) absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC (all histologies). | 3 |
| Part A Cohort 2 and Part B: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology. | 61 |
| Part C: 800 mg Neci + 200 mg Pembro Participants received 200 mg pembrolizumab absolute dose by intravenous (IV) infusion on Day 1 of 21 days cycles followed by 800 mg necitumumab absolute dose by IV infusion on Days 1 and 8 of 21 days cycles in participants with Stage IV NSCLC of squamous and nonsquamous histology.
Part C were Japan participants. | 7 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 15 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Sponsor Decision | 2 | 10 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Part A Cohort 2 and Part B: 800 mg Neci + 200 mg Pembro | Part C: 800 mg Neci + 200 mg Pembro | Total |
|---|---|---|---|---|
| Age, Continuous Part A and B | 67.0 years STANDARD_DEVIATION 7.21 | 63.13 years STANDARD_DEVIATION 9.82 | NA years | 63.31 years STANDARD_DEVIATION 9.73 |
| Age, Continuous Part C | NA years | NA years | 64.14 years STANDARD_DEVIATION 8.55 | 64.14 years STANDARD_DEVIATION 8.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 21 Participants | 0 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 39 Participants | 7 Participants | 48 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 7 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 13 Participants | 0 Participants | 13 Participants |
| Race (NIH/OMB) White | 3 Participants | 47 Participants | 0 Participants | 50 Participants |
| Region of Enrollment France | 2 Participants | 40 Participants | 0 Participants | 42 Participants |
| Region of Enrollment Japan | 0 Participants | 0 Participants | 7 Participants | 7 Participants |
| Region of Enrollment Spain | 1 Participants | 14 Participants | 0 Participants | 15 Participants |
| Region of Enrollment United States | 0 Participants | 7 Participants | 0 Participants | 7 Participants |
| Sex: Female, Male Female | 1 Participants | 17 Participants | 2 Participants | 20 Participants |
| Sex: Female, Male Male | 2 Participants | 44 Participants | 5 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 23 / 68 |
| other Total, other adverse events | 3 / 3 | 66 / 68 |
| serious Total, serious adverse events | 1 / 3 | 30 / 68 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs) in Part A and Part C
A dose limiting toxicity (DLT) was defined as an adverse event (AE) during the first 21 days that was possibly related to the study drug and fulfilled any of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0: Grade 3 or 4 nonhematologic toxicity, Grade 4 nausea, vomiting, or diarrhea that persists more than 3 days despite maximal supportive intervention, Grade 3 thrombocytopenia with bleeding requiring transfusion, Grade 4 thrombocytopenia with or without bleeding, Grade 4 neutropenia that persists more than 5 days, Grade 3 or 4 neutropenia with fever, Grade ≥3 skin toxicity despite best supportive care with some exceptions, if a total at least 75% of the planned dose for both agents cannot be administered in the first cycle due to toxicity, prolonged delay (\>2 weeks) in initiating cycle 2 due to treatment-related toxicity and Grade 5 toxicity.
Time frame: Baseline through Cycle 1 (21 day cycles)
Population: All participants who received at least one dose of study drug in Part A and Part C.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Number of Participants With Dose Limiting Toxicities (DLTs) in Part A and Part C | 0 Participants |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Number of Participants With Dose Limiting Toxicities (DLTs) in Part A and Part C | 0 Participants |
| Part C: 800 mg Neci + 200 mg Pembro | Number of Participants With Dose Limiting Toxicities (DLTs) in Part A and Part C | 0 Participants |
Primary
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) in Part A and Part B
ORR was the percentage of participants achieving a best overall response (BOR) 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 non-target lesions, and no appearance of new lesions. Progressive disease (PD) is defined as 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: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 16 Months)
Population: All participants who received at least one dose of study drug in Part A and Part B. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) in Part A and Part B | 66.7 Percentage of Participants |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) in Part A and Part B | 21.3 Percentage of Participants |
p-value: 0.4491Fisher Exact
Secondary
Duration of Response (DoR) in Part A Cohort 2 and Part B
DOR was defined only for responders (participants with confirmed CR or PR). It was measured from the date of first evidence of a confirmed CR or PR to the date of objective progression or the date of death due to any cause, whichever was earlier.
Time frame: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up To 16 Months)
Population: All participants who received at least one dose of study drug who had evaluable data in Part A Cohort 2 and Part B. 11 participants were censored. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Duration of Response (DoR) in Part A Cohort 2 and Part B | 10.94 months |
Secondary
Number of Participants With Anti-Necitumumab Antibodies in Part A, Part B and Part C
Result is considered as treatment emergent anti-necitumumab antibody positive if postbaseline titer = 4\*baseline titer for baseline titer \> 0 or if postbaseline titer \>= 20 for samples with antibody not detected.
Time frame: Predose Cycle 1 Day 1 through Predose Cycle 8 Day 1 (21 Day Cycles)
Population: All participants who received at least one dose of study drug who had evaluable data in Part A, Part B and Part C.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Number of Participants With Anti-Necitumumab Antibodies in Part A, Part B and Part C | 0 Participants |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Number of Participants With Anti-Necitumumab Antibodies in Part A, Part B and Part C | 2 Participants |
| Part C: 800 mg Neci + 200 mg Pembro | Number of Participants With Anti-Necitumumab Antibodies in Part A, Part B and Part C | 0 Participants |
Secondary
Overall Survival (OS) in Part A Cohort 2, Part B
OS duration was measured from the date of first dose of study drug (necitumumab and/or pembrolizumab) to the date of death from any cause.
Time frame: Baseline to Death from Any Cause (Up To 16 Months)
Population: All participants who received at least one dose of study drug in Part A Cohort 2 and Part B. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Overall Survival (OS) in Part A Cohort 2, Part B | NA months |
Secondary
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) in Part A Cohort 2, Part B and Part C
ORR was the percentage of participants achieving a best overall response (BOR) 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 non-target lesions, and no appearance of new lesions. PD is defined as 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: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 40 Months)
Population: All participants who received at least one dose of study drug in Part A Cohort 2, Part B and Part C. Part C were Japan participants. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) in Part A Cohort 2, Part B and Part C | 25.0 percentage of participants |
Secondary
Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR]) in Part A Cohort 2 and Part B
Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by 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 non-target lesions, and no appearance of new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. PD is defined as 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: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 16 Months)
Population: All participants who received at least one dose of study drug in Part A Cohort 2 and Part B. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR]) in Part A Cohort 2 and Part B | 62.3 percentage of participants |
Secondary
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab.
Time frame: Predose sample (within 1 hour before infusion) and postdose sample (within 10 min after infusion) on Day 1 at Cycles 1, 2, 4, 6, 8; 30 days post treatment discontinuation
Population: All participants who received at least one dose of study drug and had evaluable PK data in Part A, Part B and Part C.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 8 | 291 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 20.8 |
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 6 | 234 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 26.3 |
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 4 | 246 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 28.7 |
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 2 | 194 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 29 |
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 6 | 89.5 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 24.7 |
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 2 | 50.4 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 54.7 |
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 1 | 152 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 32.1 |
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 4 | 79.2 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 32.5 |
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 8 | 98.5 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 3.73 |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 2 | 352 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 25.3 |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 2 | 70 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 49.7 |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 6 | 195 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 12.2 |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 4 | 353 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 45.3 |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 6 | 396 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 8.53 |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 8 | 526 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 8.49 |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 4 | 148 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 32.1 |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 8 | 155 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 33 |
| Part A Cohort 2: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 1 | 269 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 15.6 |
| Part C: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 1 | 226 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 24.6 |
| Part C: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 8 | 91 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 62.7 |
| Part C: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 8 | 295 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 46.4 |
| Part C: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 6 | 114 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 58.3 |
| Part C: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 4 | 315 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 45.4 |
| Part C: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 4 | 101 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 48 |
| Part C: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 2 | 273 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 36.8 |
| Part C: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 2 | 58.2 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 56 |
| Part C: 800 mg Neci + 200 mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 6 | 312 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 42.1 |
| Part C: 800mg Neci + 200mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 2 | 90.4 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 18.4 |
| Part C: 800mg Neci + 200mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 8 | 507 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 7.95 |
| Part C: 800mg Neci + 200mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 6 | 114 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 66.5 |
| Part C: 800mg Neci + 200mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 1 | 281 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 26 |
| Part C: 800mg Neci + 200mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 4 | 136 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 9.51 |
| Part C: 800mg Neci + 200mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 6 | 406 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 12.9 |
| Part C: 800mg Neci + 200mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | Pre-Dose Cycle 8 | 209 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 18.7 |
| Part C: 800mg Neci + 200mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 4 | 428 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 5.18 |
| Part C: 800mg Neci + 200mg Pembro | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab in Part A, Part B and Part C | End-of-Infusion Cycle 2 | 391 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 25.4 |
Secondary
Progression Free Survival (PFS) in Part A Cohort 2 and Part B
PFS was defined as the time from the date of first dose of study drug until first observation of objective (radiographically documented) PD as defined by RECIST v1.1 or death from any cause, whichever comes first. PD is defined as 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: Baseline to Measured Progressive Disease or Death Due to Any Cause (Up To 16 Months)
Population: All participants who received at least one dose of study drug and who had evaluable data in Part A Cohort 2 and Part B. 21 participants were censored. Per protocol, participants in Part A cohort 2 who received the recommended necitumumab dose for Part B were also analyzed together with Part B.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A Cohort 1: 600 mg Neci + 200 mg Pembro | Progression Free Survival (PFS) in Part A Cohort 2 and Part B | 3.98 Months |