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A Study of Necitumumab and Abemaciclib in Participants With Non-Small Cell Lung Cancer (NSCLC)

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02411591
Collaborator
(none)
66
Enrollment
15
Locations
1
Arm
47.8
Actual Duration (Months)
4.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
66 participants
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Single-Arm, Multicenter, Phase 1b Study With an Expansion Cohort to Evaluate Safety and Efficacy of Necitumumab in Combination With Abemaciclib in Treatment of Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)
Actual Study Start Date :
Jun 4, 2015
Actual Primary Completion Date :
Jun 23, 2017
Actual Study Completion Date :
May 28, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Necitumumab + Abemaciclib

Cohort 1 Part A: Necitumumab 800 mg administered intravenously (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. Cohort 2 Part A: Necitumumab 800 mg administered IV on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. Treatment may continue until discontinuation criterion is met. Cohort 3 Part A: Necitumumab 800 mg administered IV on Days 1 and 8, followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. Treatment may continue until discontinuation criterion is met. Part B (expansion cohort): Necitumumab 800 mg administered IV on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. Treatment may continue until discontinuation criterion is met.

Drug: Necitumumab
Administered IV.
Other Names:
  • LY3012211

    • Drug: Abemaciclib
    Administered orally.
    Other Names:
  • LY2835219

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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 Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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)

    6. 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.

    7. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician. Charleroi Belgium 6000
    2 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician. Leuven Belgium 3000
    3 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician. Roeselare Belgium 8800
    4 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician. Brest France 29609
    5 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician. Bron France 69677
    6 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Lille France 59037
    7 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Lyon France 69373
    8 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician. Marseille Cedex 05 France 13385
    9 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician. Montpellier France 34295
    10 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician. Pau France 64046
    11 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Strasbourg Cedex France 67091
    12 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician. Villejuif France 94805
    13 Hospital Universitario Ramon y Cajal Madrid Spain 28034
    14 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Madrid Spain 28040
    15 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Sevilla Spain 46014

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT02411591
    Other Study ID Numbers:
    • 15573
    • I4X-MC-JFCU
    First Posted:
    Apr 8, 2015
    Last Update Posted:
    Jul 9, 2020
    Last Verified:
    Jul 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Carcinoma, Non-Small-Cell Lung
    Neoplasm Metastasis
    Necitumumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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.
    Arm/Group Title Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)
    Arm/Group Description Part A: Necitumumab 800 milligram (mg) was administered intravenously (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. Part A: Necitumumab 800 mg administered IV on Days 1 and 8, followed by abemaciclib 150 mg 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 800 mg administered IV on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.
    Period Title: Overall Study
    STARTED 3 57 6
    Part A 3 6 6
    Expansion Cohort Part B 0 51 0
    Progressive Disease 3 42 3
    Death 0 2 0
    COMPLETED 3 47 3
    NOT COMPLETED 0 10 3

    Baseline Characteristics

    Arm/Group Title 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
    Arm/Group Description 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. 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. 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. Total of all reporting groups
    Overall Participants 3 57 6 66
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    62.33
    (2.31)
    61.42
    (10.58)
    49.00
    (7.59)
    60.33
    (10.68)
    Sex: Female, Male (Count of Participants)
    Female
    1
    33.3%
    17
    29.8%
    1
    16.7%
    19
    28.8%
    Male
    2
    66.7%
    40
    70.2%
    5
    83.3%
    47
    71.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    2
    3.5%
    0
    0%
    2
    3%
    Not Hispanic or Latino
    1
    33.3%
    13
    22.8%
    1
    16.7%
    15
    22.7%
    Unknown or Not Reported
    2
    66.7%
    42
    73.7%
    5
    83.3%
    49
    74.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    1
    33.3%
    16
    28.1%
    1
    16.7%
    18
    27.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    2
    66.7%
    41
    71.9%
    5
    83.3%
    48
    72.7%
    Region of Enrollment (Count of Participants)
    Belgium
    1
    33.3%
    9
    15.8%
    1
    16.7%
    11
    16.7%
    France
    2
    66.7%
    45
    78.9%
    5
    83.3%
    52
    78.8%
    Spain
    0
    0%
    3
    5.3%
    0
    0%
    3
    4.5%

    Outcome Measures

    1. Primary Outcome
    Title Part A: Number of Participants With Abemaciclib Dose Limiting Toxicities (DLTs)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug and had evaluable DLTs.
    Arm/Group Title Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) Cohort 3 (Necitumamab 800 mg + Abemaciclib 200 mg)
    Arm/Group Description 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. Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.
    Measure Participants 3 6 6
    Count of Participants [Participants]
    0
    0%
    1
    1.8%
    3
    50%
    2. Primary Outcome
    Title Progression Free Survival (PFS) Rate at 3 Months (Percentage of Participants With PFS at 3 Months)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)
    Arm/Group Description 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. Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 150 mg 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 800 mg administered IV on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.
    Measure Participants 3 57 6
    Number (95% Confidence Interval) [percentage of participants]
    66.7
    2223.3%
    32.3
    56.7%
    50.0
    833.3%
    3. Secondary Outcome
    Title Percentage of Participants Who Achieve Best Overall Tumor Response of Complete or Partial Response (Objective Response Rate [ORR])
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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 Enrolled Participants (Necitumumab + Abemaciclib)
    Arm/Group Description 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. Part A: Necitumumab 800 mg administered intravenously (IV) on Days 1 and 8, followed by abemaciclib 150 mg 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 800 mg administered IV on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Cohorts 1, 2 and 3 combined. Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 100 mg, 150 mg or 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.
    Measure Participants 3 57 6 66
    Overall Response Rate
    66.7
    2223.3%
    5.3
    9.3%
    0.0
    0%
    7.6
    11.5%
    PR
    66.7
    2223.3%
    5.3
    9.3%
    0.0
    0%
    7.6
    11.5%
    SD
    33.3
    1110%
    42.1
    73.9%
    66.7
    1111.7%
    43.9
    66.5%
    PD
    0.0
    0%
    47.4
    83.2%
    16.7
    278.3%
    42.4
    64.2%
    4. Secondary Outcome
    Title Pharmacokinetics (PK): Predose Concentration (Cmin) of Necitumumab
    Description 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

    Outcome Measure Data

    Analysis Population Description
    All participants who received same dose of necitumumab, pre-specified to assess as single group and had evaluable PK data.
    Arm/Group Title Necitumumab
    Arm/Group Description Necitumumab 800 mg was administered IV on Days 1 and 8, of a 3-week cycle.
    Measure Participants 61
    Cycle 1, Day 8
    64.1
    (43.1)
    Cycle 2, Day 1
    49.6
    (63.8)
    Cycle 3, Day 1
    93.8
    (44.1)
    Cycle 5, Day 1
    160
    (50.3)
    Cycle 7, Day 1
    165
    (42.1)
    5. Secondary Outcome
    Title Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab
    Description 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

    Outcome Measure Data

    Analysis Population Description
    All participants who received same dose of necitumumab, pre-specified to assess as single group and had evaluable PK data.
    Arm/Group Title Necitumumab
    Arm/Group Description Necitumumab 800 mg was administered IV on Days 1 and 8, of a 3-week cycle.
    Measure Participants 61
    Cycle 1, Day 1
    228
    (45.6)
    Cycle 1, Day 8 (D8)
    304
    (21.9)
    Cycle 2, Day 1
    270
    (25.6)
    Cycle 3, Day 1
    318
    (43.7)
    Cycle 5, Day 1
    356
    (42.7)
    Cycle 7, Day 1
    350
    (24.7)
    6. Secondary Outcome
    Title Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib
    Description 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

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of abemaciclib and had evaluable PK data for Part A.
    Arm/Group Title Abemaciclib 100 mg Abemaciclib 150 mg Abemaciclib 200 mg
    Arm/Group Description Necitumumab 800 mg 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. Necitumumab 800 mg administered IV on Days 1 and 8 followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Necitumumab 800 mg administered IV on Days 1 and 8 followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.
    Measure Participants 3 5 5
    Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter (ng/mL)]
    15.6
    (146)
    26
    (148)
    38.2
    (80)
    7. Secondary Outcome
    Title Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) From Zero to the Last Time Point (AUC[0-tlast]) Abemaciclib
    Description 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

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of abemaciclib and had evaluable PK data for Part A.
    Arm/Group Title Abemaciclib 100 mg Abemaciclib 150 mg Abemaciclib 200 mg
    Arm/Group Description Necitumumab 800 mg 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. Necitumumab 800 mg administered IV on Days 1 and 8 followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Necitumumab 800 mg administered IV on Days 1 and 8 followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.
    Measure Participants 3 5 5
    Geometric Mean (Geometric Coefficient of Variation) [hour*nanogram/milliliter (hr*ng/mL)]
    118
    (200)
    209
    (136)
    336
    (83)
    8. Secondary Outcome
    Title Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR])
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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 Enrolled Participants (Necitumumab + Abemaciclib)
    Arm/Group Description 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. Part A: Necitumumab 800 mg administered intravenously (IV) on Days 1 and 8, followed by abemaciclib 150 mg 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 800 mg administered IV on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Cohorts 1, 2 and 3 combined. Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 100 mg, 150 mg or 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.
    Measure Participants 3 57 6 66
    Number (95% Confidence Interval) [percentage of participants]
    100
    3333.3%
    47.4
    83.2%
    66.7
    1111.7%
    51.5
    78%
    9. Secondary Outcome
    Title Overall Survival
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Cohort 1 (Necitumumab 800 mg + Abemaciclib 100 mg) Cohort 2 (Necitumumab 800 mg + Abemaciclib 150 mg) Cohort 3 (Necitumumab 800 mg + Abemaciclib 200 mg)
    Arm/Group Description 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. Part A: Necitumumab 800 mg administered intravenously (IV) on Days 1 and 8, followed by abemaciclib 150 mg 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 800 mg administered IV on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Part A: Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.
    Measure Participants 3 57 6
    Median (95% Confidence Interval) [Months]
    NA
    6.93
    13.45

    Adverse Events

    Time Frame Up to 21 Months
    Adverse Event Reporting Description All enrolled participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
    Arm/Group Title Necitumumab 800 mg + Abemaciclib 100 mg Necitumumab 800 mg + Abemaciclib 150 mg Necitumumab 800 mg + Abemaciclib 200 mg
    Arm/Group Description 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. Necitumumab 800 mg administered intravenously (IV) on Days 1 and 8, followed by abemaciclib 150 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met. Necitumumab 800 mg was administered IV on Days 1 and 8, followed by abemaciclib 200 mg given orally every 12 hours on Days 1 to 21. (21 day cycles.) Treatment may continue until discontinuation criterion is met.
    All Cause Mortality
    Necitumumab 800 mg + Abemaciclib 100 mg Necitumumab 800 mg + Abemaciclib 150 mg Necitumumab 800 mg + Abemaciclib 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 5/57 (8.8%) 2/6 (33.3%)
    Serious Adverse Events
    Necitumumab 800 mg + Abemaciclib 100 mg Necitumumab 800 mg + Abemaciclib 150 mg Necitumumab 800 mg + Abemaciclib 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/3 (66.7%) 25/57 (43.9%) 4/6 (66.7%)
    Blood and lymphatic system disorders
    Thrombocytopenia 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Cardiac disorders
    Atrial flutter 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Eye disorders
    Blindness 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Gastrointestinal disorders
    Diarrhoea 0/3 (0%) 0 2/57 (3.5%) 2 0/6 (0%) 0
    Nausea 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Vomiting 0/3 (0%) 0 5/57 (8.8%) 6 0/6 (0%) 0
    General disorders
    Fatigue 0/3 (0%) 0 2/57 (3.5%) 2 0/6 (0%) 0
    General physical health deterioration 0/3 (0%) 0 2/57 (3.5%) 2 0/6 (0%) 0
    Pyrexia 0/3 (0%) 0 2/57 (3.5%) 2 1/6 (16.7%) 1
    Vascular stent thrombosis 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Infections and infestations
    Anal abscess 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Device related infection 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Erysipelas 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Lung infection 0/3 (0%) 0 2/57 (3.5%) 2 0/6 (0%) 0
    Pneumonia 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Respiratory tract infection 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Urinary tract infection 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Injury, poisoning and procedural complications
    Infusion related reaction 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Investigations
    Blood creatinine increased 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Hypokalaemia 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Nervous system disorders
    Headache 0/3 (0%) 0 2/57 (3.5%) 2 0/6 (0%) 0
    Loss of consciousness 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Somnolence 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/3 (0%) 0 1/57 (1.8%) 2 0/6 (0%) 0
    Hydronephrosis 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Renal failure 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Ureterolithiasis 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/3 (0%) 0 1/57 (1.8%) 2 0/6 (0%) 0
    Pneumomediastinum 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Pneumonitis 0/3 (0%) 0 2/57 (3.5%) 2 0/6 (0%) 0
    Pulmonary embolism 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Skin and subcutaneous tissue disorders
    Palmar-plantar erythrodysaesthesia syndrome 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Vascular disorders
    Phlebitis 0/3 (0%) 0 1/57 (1.8%) 1 0/6 (0%) 0
    Superior vena cava syndrome 0/3 (0%) 0 1/57 (1.8%) 2 0/6 (0%) 0
    Other (Not Including Serious) Adverse Events
    Necitumumab 800 mg + Abemaciclib 100 mg Necitumumab 800 mg + Abemaciclib 150 mg Necitumumab 800 mg + Abemaciclib 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 57/57 (100%) 6/6 (100%)
    Blood and lymphatic system disorders
    Anaemia 1/3 (33.3%) 1 21/57 (36.8%) 45 3/6 (50%) 4
    Leukocytosis 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Leukopenia 0/3 (0%) 0 1/57 (1.8%) 1 1/6 (16.7%) 1
    Lymphopenia 0/3 (0%) 0 3/57 (5.3%) 3 1/6 (16.7%) 1
    Thrombocytopenia 0/3 (0%) 0 5/57 (8.8%) 9 2/6 (33.3%) 2
    Cardiac disorders
    Arrhythmia 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Sinus tachycardia 1/3 (33.3%) 1 2/57 (3.5%) 2 0/6 (0%) 0
    Eye disorders
    Cataract 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Dry eye 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Lacrimation increased 1/3 (33.3%) 1 2/57 (3.5%) 3 0/6 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 0/3 (0%) 0 7/57 (12.3%) 7 0/6 (0%) 0
    Abdominal pain upper 0/3 (0%) 0 3/57 (5.3%) 3 1/6 (16.7%) 1
    Ascites 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Constipation 1/3 (33.3%) 1 8/57 (14%) 8 0/6 (0%) 0
    Dental caries 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Diarrhoea 1/3 (33.3%) 1 29/57 (50.9%) 49 3/6 (50%) 6
    Dry mouth 0/3 (0%) 0 2/57 (3.5%) 2 1/6 (16.7%) 1
    Dysphagia 0/3 (0%) 0 4/57 (7%) 4 0/6 (0%) 0
    Haemorrhoidal haemorrhage 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Nausea 0/3 (0%) 0 24/57 (42.1%) 32 3/6 (50%) 3
    Stomatitis 0/3 (0%) 0 7/57 (12.3%) 8 3/6 (50%) 5
    Tooth discolouration 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Vomiting 1/3 (33.3%) 1 16/57 (28.1%) 24 3/6 (50%) 4
    General disorders
    Asthenia 1/3 (33.3%) 1 8/57 (14%) 12 1/6 (16.7%) 1
    Fatigue 2/3 (66.7%) 6 29/57 (50.9%) 49 3/6 (50%) 4
    General physical health deterioration 0/3 (0%) 0 4/57 (7%) 4 0/6 (0%) 0
    Mucosal dryness 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Oedema peripheral 1/3 (33.3%) 1 3/57 (5.3%) 3 1/6 (16.7%) 1
    Pain 0/3 (0%) 0 5/57 (8.8%) 5 0/6 (0%) 0
    Pyrexia 2/3 (66.7%) 3 10/57 (17.5%) 10 2/6 (33.3%) 2
    Xerosis 1/3 (33.3%) 1 4/57 (7%) 4 0/6 (0%) 0
    Hepatobiliary disorders
    Cholestasis 0/3 (0%) 0 2/57 (3.5%) 2 1/6 (16.7%) 1
    Infections and infestations
    Anal abscess 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Bronchitis 0/3 (0%) 0 4/57 (7%) 5 0/6 (0%) 0
    Conjunctivitis 1/3 (33.3%) 1 5/57 (8.8%) 5 1/6 (16.7%) 1
    Folliculitis 0/3 (0%) 0 5/57 (8.8%) 8 1/6 (16.7%) 1
    Fungal skin infection 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Nail infection 1/3 (33.3%) 3 0/57 (0%) 0 0/6 (0%) 0
    Paronychia 2/3 (66.7%) 3 6/57 (10.5%) 9 3/6 (50%) 3
    Pharyngitis 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Tinea pedis 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Upper respiratory tract infection 1/3 (33.3%) 1 2/57 (3.5%) 2 0/6 (0%) 0
    Urinary tract infection 0/3 (0%) 0 3/57 (5.3%) 3 0/6 (0%) 0
    Injury, poisoning and procedural complications
    Contusion 1/3 (33.3%) 2 0/57 (0%) 0 0/6 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/3 (0%) 0 5/57 (8.8%) 6 0/6 (0%) 0
    Aspartate aminotransferase increased 0/3 (0%) 0 3/57 (5.3%) 4 0/6 (0%) 0
    Blood creatinine increased 0/3 (0%) 0 13/57 (22.8%) 23 1/6 (16.7%) 1
    Neutrophil count decreased 0/3 (0%) 0 9/57 (15.8%) 18 0/6 (0%) 0
    Platelet count decreased 0/3 (0%) 0 11/57 (19.3%) 28 1/6 (16.7%) 1
    Weight decreased 0/3 (0%) 0 7/57 (12.3%) 9 1/6 (16.7%) 2
    Metabolism and nutrition disorders
    Decreased appetite 2/3 (66.7%) 3 21/57 (36.8%) 24 4/6 (66.7%) 7
    Hyperglycaemia 1/3 (33.3%) 1 1/57 (1.8%) 1 1/6 (16.7%) 1
    Hyperkalaemia 0/3 (0%) 0 3/57 (5.3%) 3 0/6 (0%) 0
    Hypoalbuminaemia 0/3 (0%) 0 4/57 (7%) 4 2/6 (33.3%) 2
    Hypocalcaemia 0/3 (0%) 0 1/57 (1.8%) 1 1/6 (16.7%) 1
    Hypochloraemia 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Hypokalaemia 1/3 (33.3%) 2 12/57 (21.1%) 17 4/6 (66.7%) 5
    Hypomagnesaemia 0/3 (0%) 0 20/57 (35.1%) 29 1/6 (16.7%) 3
    Hyponatraemia 0/3 (0%) 0 4/57 (7%) 7 2/6 (33.3%) 2
    Hypophosphataemia 0/3 (0%) 0 8/57 (14%) 18 1/6 (16.7%) 2
    Musculoskeletal and connective tissue disorders
    Arthritis 1/3 (33.3%) 1 1/57 (1.8%) 1 0/6 (0%) 0
    Back pain 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Bursitis 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Musculoskeletal pain 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Neck pain 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Osteoporosis 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Pain in extremity 1/3 (33.3%) 1 1/57 (1.8%) 1 1/6 (16.7%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pyogenic granuloma 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Tumour pain 1/3 (33.3%) 1 5/57 (8.8%) 5 0/6 (0%) 0
    Nervous system disorders
    Disturbance in attention 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Dysgeusia 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Headache 1/3 (33.3%) 1 6/57 (10.5%) 6 3/6 (50%) 3
    Paraesthesia 1/3 (33.3%) 1 1/57 (1.8%) 1 1/6 (16.7%) 1
    Peripheral sensory neuropathy 0/3 (0%) 0 1/57 (1.8%) 1 1/6 (16.7%) 1
    Psychiatric disorders
    Anxiety 1/3 (33.3%) 1 0/57 (0%) 0 1/6 (16.7%) 1
    Depression 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Insomnia 0/3 (0%) 0 5/57 (8.8%) 5 0/6 (0%) 0
    Renal and urinary disorders
    Dysuria 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Ureterolithiasis 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Reproductive system and breast disorders
    Vaginal discharge 0/1 (0%) 0 1/17 (5.9%) 1 0/1 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 0/3 (0%) 0 10/57 (17.5%) 10 1/6 (16.7%) 1
    Dysphonia 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Dyspnoea 1/3 (33.3%) 1 21/57 (36.8%) 21 1/6 (16.7%) 3
    Epistaxis 1/3 (33.3%) 2 0/57 (0%) 0 2/6 (33.3%) 2
    Haemoptysis 0/3 (0%) 0 3/57 (5.3%) 3 0/6 (0%) 0
    Laryngeal inflammation 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0
    Pleural effusion 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform 2/3 (66.7%) 6 26/57 (45.6%) 41 3/6 (50%) 5
    Dry skin 2/3 (66.7%) 3 15/57 (26.3%) 20 4/6 (66.7%) 4
    Nail ridging 0/3 (0%) 0 1/57 (1.8%) 1 1/6 (16.7%) 1
    Palmar-plantar erythrodysaesthesia syndrome 0/3 (0%) 0 3/57 (5.3%) 9 0/6 (0%) 0
    Petechiae 0/3 (0%) 0 0/57 (0%) 0 1/6 (16.7%) 1
    Pruritus 1/3 (33.3%) 1 5/57 (8.8%) 7 0/6 (0%) 0
    Rash 0/3 (0%) 0 8/57 (14%) 23 1/6 (16.7%) 1
    Rash maculo-papular 0/3 (0%) 0 4/57 (7%) 4 0/6 (0%) 0
    Skin fissures 1/3 (33.3%) 2 1/57 (1.8%) 1 0/6 (0%) 0
    Skin ulcer 1/3 (33.3%) 1 1/57 (1.8%) 1 0/6 (0%) 0
    Vascular disorders
    Hypotension 1/3 (33.3%) 1 1/57 (1.8%) 1 0/6 (0%) 0
    Intermittent claudication 1/3 (33.3%) 1 0/57 (0%) 0 0/6 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email ClinicalTrials.gov@lilly.com
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT02411591
    Other Study ID Numbers:
    • 15573
    • I4X-MC-JFCU
    First Posted:
    Apr 8, 2015
    Last Update Posted:
    Jul 9, 2020
    Last Verified:
    Jul 1, 2019