Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis
Conditions
Brief summary
This is medical research evaluating the safety and efficacy of two new medicines (necitumumab and abemaciclib), administered in combination in participants affected by a defined type of advanced lung cancer (stage IV non-small-cell lung cancer).
Interventions
DRUGNecitumumab
Administered IV.
DRUGAbemaciclib
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed NSCLC Stage IV: * Part A: NSCLC Stage IV (any type). * Part B: NSCLC Stage IV (squamous and nonsquamous). * 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 must have progressed after platinum-based chemotherapy AND have received a maximum of 1 other prior chemotherapy for advanced and/or metastatic disease OR must be judged by the physician as ineligible for further standard second-line chemotherapy. Prior treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) and anaplastic lymphoma kinase (ALK) inhibitors is mandatory in participants whose tumor has EGFR-activating mutations or ALK translocations. Prior targeting agents and neoadjuvant/adjuvant therapies are permitted with the exception of cyclin-dependent kinase (CDK)4/6-targeting agents or necitumumab. * The participant has tumor tissue available for biomarker analyses. * The participant has an Eastern Cooperative Oncology Group performance status score of 0-1. * Have adequate organ functions.
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 cyclin-dependent kinase 4 and 6 (CDK4/6) - targeting agents or necitumumab is not permitted. * Have a serious concomitant systemic disorder or significant cardiac disease. * The participant has undergone major surgery or received any investigational therapy in the 30-days prior to study enrollment. * The participant has undergone chest irradiation within 4 weeks prior to receiving study treatment. * The participant has brain metastases that are symptomatic. * History of arterial or venous thromboembolism within 3 months prior to study enrollment. Participants with a history of venous thromboembolism beyond 3 months prior to study enrollment can be enrolled if they are appropriately treated with low molecular weight heparin. * The participant has active infection requiring systemic therapy. * 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 abemaciclib, or any other contraindication to one of the administered treatments. * The participant is pregnant or breastfeeding. * 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 or an active non-infectious pneumonitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With Abemaciclib Dose Limiting Toxicities (DLTs) | Baseline through Cycle 1 (Up to 21 Days) | A DLT was defined as one of the following adverse events (AEs), occurring in Cycle 1 if considered to be definitely, probably, or possibly related to necitumumab and abemaciclib: Grade 3 or 4 nonhematologic toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0), except for nausea, vomiting, diarrhea, or electrolyte disturbance. Grade 3 or 4 nausea, vomiting, or diarrhea that persists more than 2 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. |
| Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants With PFS at 3 Months) | Baseline to measured progressive disease or death due to any cause (3 Months) | PFS is defined as the time from baseline until first observation of progressive disease(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 millimeter (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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab | Cycle 1, Day 1 (C1D1): 0.25, 2,4,10 hours(h) post dose, C1D8: 0.25h post dose, Cycle 2, Day 1 (C2D1): 0.25, 2,4,10h post dose; C3,5,7 D1: 0.25h post dose | Maximum necitumumab concentration data following doses of 800 mg administered Day 1 and 8 of a 3-week cycle as an intravenous (IV) infusion over 60 minutes. |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib | Cycle 1, Day 1 (C1D1): 0.25, 2,4,6,8,10 hours(h) post dose, C1D8: 0.25h post dose, C2D1: 0.25, 2,4,6,8,10h post dose; C3,5,7 D1: 0.25h post dose | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib summary of LSN3106729 noncompartmental PK parameters after twice daily oral dose of Abemaciclib. |
| Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | Baseline to measured progressive disease or start of new anti-cancer therapy (up to 21 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. 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. Confidence intervals are based on Clopper-Pearson method. |
| Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR]) | Baseline to measured progressive disease or start of new anti-cancer therapy (up to 21 months) | Disease Control Rate (DCR) is defined as the percentage of participants achieving a best overall response of stable disease (SD), PR, or CR. DCR used the same denominator as defined in ORR. Among participants counted in the denominator, the numerator counted those with a confirmed best tumor response of SD, PR, or CR per RECIST v1.1. Confidence intervals are based on Clopper-Pearson method. |
| Overall Survival | Baseline to date of death from any cause (24 Months) | Overall survival (OS) is defined as the time from the date of study enrollment to the date of death from any cause. For each participant who is not known to have died as of the data -inclusion cutoff date for a particular analysis, OS was censored for that analysis at the last known alive date. |
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib | Cycle 1, Day 1 (C1D1): 0.25, 2,4,6,8,10 hours(h) post dose | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC\[0-tlast\]) summary of LSN3106729 noncompartmental PK parameters after twice daily oral dose of Abemaciclib. (tlast = 10 hours) |
| Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab | Cycle 1, Day 8 (C1D8) and C2,3,5,7 D1: Predose | Predose necitumumab concentration data following doses of 800 mg administered Day 1 and 8 of a 3-week cycle as an intravenous (IV) infusion over 60 minutes. |
Countries
Belgium, France, Spain
Participant flow
Pre-assignment details
The study has 2 parts (Part A and Part B). Part A is a dose-escalation study to determine the recommended dose of abemaciclib in combination with necitumumab Part B (expansion cohort). Completers completed the 2 cycles, with required assessment, had progressive disease or died due to any cause, alive and on study at conclusion but off treatment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 100 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. | 3 |
| Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) Part A: Necitumumab administered intravenously (IV) on Days 1 and 8, followed by abemaciclib given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.
Part B (expansion cohort) : Necitumumab administered IV on Days 1 and 8, followed by abemaciclib given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. | 57 |
| Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg) Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 200 mg given orally Q12H on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. | 6 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 | 2 |
| Overall Study | Physician Decision | 0 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) | Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg) | Total |
|---|---|---|---|---|
| Age, Continuous | 62.33 years STANDARD_DEVIATION 2.31 | 61.42 years STANDARD_DEVIATION 10.58 | 49.00 years STANDARD_DEVIATION 7.59 | 60.33 years STANDARD_DEVIATION 10.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 13 Participants | 1 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 42 Participants | 5 Participants | 49 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 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 | 2 Participants | 41 Participants | 5 Participants | 48 Participants |
| Race (NIH/OMB) White | 1 Participants | 16 Participants | 1 Participants | 18 Participants |
| Region of Enrollment Belgium | 1 Participants | 9 Participants | 1 Participants | 11 Participants |
| Region of Enrollment France | 2 Participants | 45 Participants | 5 Participants | 52 Participants |
| Region of Enrollment Spain | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 17 Participants | 1 Participants | 19 Participants |
| Sex: Female, Male Male | 2 Participants | 40 Participants | 5 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 5 / 57 | 2 / 6 |
| other Total, other adverse events | 3 / 3 | 57 / 57 | 6 / 6 |
| serious Total, serious adverse events | 2 / 3 | 25 / 57 | 4 / 6 |
Outcome results
Primary
Part A: Number of Participants With Abemaciclib Dose Limiting Toxicities (DLTs)
A DLT was defined as one of the following adverse events (AEs), occurring in Cycle 1 if considered to be definitely, probably, or possibly related to necitumumab and abemaciclib: Grade 3 or 4 nonhematologic toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0), except for nausea, vomiting, diarrhea, or electrolyte disturbance. Grade 3 or 4 nausea, vomiting, or diarrhea that persists more than 2 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.
Time frame: Baseline through Cycle 1 (Up to 21 Days)
Population: All participants who received at least one dose of study drug and had evaluable DLTs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Part A: Number of Participants With Abemaciclib Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) | Part A: Number of Participants With Abemaciclib Dose Limiting Toxicities (DLTs) | 1 Participants |
| Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) | Part A: Number of Participants With Abemaciclib Dose Limiting Toxicities (DLTs) | 3 Participants |
Primary
Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants With PFS at 3 Months)
PFS is defined as the time from baseline until first observation of progressive disease(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 millimeter (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: Baseline to measured progressive disease or death due to any cause (3 Months)
Population: All enrolled participants who received at least one dose of study drug and had evaluable PFS data. Cohort 2 number of censored participants is 10. Cohort 2 includes total number of participants in Part A and evaluable participants of Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants With PFS at 3 Months) | 66.7 percentage of participants |
| Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) | Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants With PFS at 3 Months) | 32.3 percentage of participants |
| Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) | Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants With PFS at 3 Months) | 50.0 percentage of participants |
Secondary
Overall Survival
Overall survival (OS) is defined as the time from the date of study enrollment to the date of death from any cause. For each participant who is not known to have died as of the data -inclusion cutoff date for a particular analysis, OS was censored for that analysis at the last known alive date.
Time frame: Baseline to date of death from any cause (24 Months)
Population: All enrolled participants who received at least one dose of study drug and had evaluable overall survival (OS) data. Cohort 2 includes total number of participants in Part A and evaluable participants of Part B. Participants censored in cohort 1 = 2, cohort 2 = 1 and cohort 3 = 21.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Overall Survival | NA Months |
| Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) | Overall Survival | 6.93 Months |
| Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) | Overall Survival | 13.45 Months |
Secondary
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective 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. 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. Confidence intervals are based on Clopper-Pearson method.
Time frame: Baseline to measured progressive disease or start of new anti-cancer therapy (up to 21 months)
Population: All enrolled participants who received at least one dose of study drug and had evaluable ORR data in cohorts 1, 2 and 3. Cohort 2 includes total number of participants in Part A and evaluable participants of Part B.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | Overall Response Rate | 66.7 percentage of participants |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | PR | 66.7 percentage of participants |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | SD | 33.3 percentage of participants |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | PD | 0.0 percentage of participants |
| Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | PR | 5.3 percentage of participants |
| Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | SD | 42.1 percentage of participants |
| Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | PD | 47.4 percentage of participants |
| Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | Overall Response Rate | 5.3 percentage of participants |
| Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | SD | 66.7 percentage of participants |
| Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | PR | 0.0 percentage of participants |
| Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | PD | 16.7 percentage of participants |
| Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | Overall Response Rate | 0.0 percentage of participants |
| Total Enrolled Participants (Necitumumab + Abemaciclib) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | PD | 42.4 percentage of participants |
| Total Enrolled Participants (Necitumumab + Abemaciclib) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | PR | 7.6 percentage of participants |
| Total Enrolled Participants (Necitumumab + Abemaciclib) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | Overall Response Rate | 7.6 percentage of participants |
| Total Enrolled Participants (Necitumumab + Abemaciclib) | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR]) | SD | 43.9 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])
Disease Control Rate (DCR) is defined as the percentage of participants achieving a best overall response of stable disease (SD), PR, or CR. DCR used the same denominator as defined in ORR. Among participants counted in the denominator, the numerator counted those with a confirmed best tumor response of SD, PR, or CR per RECIST v1.1. Confidence intervals are based on Clopper-Pearson method.
Time frame: Baseline to measured progressive disease or start of new anti-cancer therapy (up to 21 months)
Population: All enrolled participants who received at least one dose of study drug and had evaluable ORR data in cohorts 1, 2 and 3.Cohort 2 includes total number of participants in Part A and evaluable participants of Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR]) | 100 percentage of participants |
| Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) | Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR]) | 47.4 percentage of participants |
| Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) | Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR]) | 66.7 percentage of participants |
| Total Enrolled Participants (Necitumumab + Abemaciclib) | Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR]) | 51.5 percentage of participants |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC\[0-tlast\]) summary of LSN3106729 noncompartmental PK parameters after twice daily oral dose of Abemaciclib. (tlast = 10 hours)
Time frame: Cycle 1, Day 1 (C1D1): 0.25, 2,4,6,8,10 hours(h) post dose
Population: All participants who received at least one dose of abemaciclib and had evaluable PK data for Part A.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib | 118 hour*nanogram/milliliter (hr*ng/mL) | Geometric Coefficient of Variation 200 |
| Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib | 209 hour*nanogram/milliliter (hr*ng/mL) | Geometric Coefficient of Variation 136 |
| Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib | 336 hour*nanogram/milliliter (hr*ng/mL) | Geometric Coefficient of Variation 83 |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib summary of LSN3106729 noncompartmental PK parameters after twice daily oral dose of Abemaciclib.
Time frame: Cycle 1, Day 1 (C1D1): 0.25, 2,4,6,8,10 hours(h) post dose, C1D8: 0.25h post dose, C2D1: 0.25, 2,4,6,8,10h post dose; C3,5,7 D1: 0.25h post dose
Population: All participants who received at least one dose of abemaciclib and had evaluable PK data for Part A.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib | 15.6 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 146 |
| Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib | 26 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 148 |
| Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib | 38.2 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 80 |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab
Maximum necitumumab concentration data following doses of 800 mg administered Day 1 and 8 of a 3-week cycle as an intravenous (IV) infusion over 60 minutes.
Time frame: Cycle 1, Day 1 (C1D1): 0.25, 2,4,10 hours(h) post dose, C1D8: 0.25h post dose, Cycle 2, Day 1 (C2D1): 0.25, 2,4,10h post dose; C3,5,7 D1: 0.25h post dose
Population: All participants who received same dose of necitumumab, pre-specified to assess as single group and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab | Cycle 1, Day 8 (D8) | 304 μg/mL | Geometric Coefficient of Variation 21.9 |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab | Cycle 2, Day 1 | 270 μg/mL | Geometric Coefficient of Variation 25.6 |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab | Cycle 3, Day 1 | 318 μg/mL | Geometric Coefficient of Variation 43.7 |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab | Cycle 1, Day 1 | 228 μg/mL | Geometric Coefficient of Variation 45.6 |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab | Cycle 5, Day 1 | 356 μg/mL | Geometric Coefficient of Variation 42.7 |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab | Cycle 7, Day 1 | 350 μg/mL | Geometric Coefficient of Variation 24.7 |
Secondary
Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab
Predose necitumumab concentration data following doses of 800 mg administered Day 1 and 8 of a 3-week cycle as an intravenous (IV) infusion over 60 minutes.
Time frame: Cycle 1, Day 8 (C1D8) and C2,3,5,7 D1: Predose
Population: All participants who received same dose of necitumumab, pre-specified to assess as single group and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab | Cycle 1, Day 8 | 64.1 microgram/milliliter (μg/mL) | Standard Deviation 43.1 |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab | Cycle 2, Day 1 | 49.6 microgram/milliliter (μg/mL) | Standard Deviation 63.8 |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab | Cycle 3, Day 1 | 93.8 microgram/milliliter (μg/mL) | Standard Deviation 44.1 |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab | Cycle 5, Day 1 | 160 microgram/milliliter (μg/mL) | Standard Deviation 50.3 |
| Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) | Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab | Cycle 7, Day 1 | 165 microgram/milliliter (μg/mL) | Standard Deviation 42.1 |