A medical research evaluating the safety and efficacy of two new medicines (Necitumumab and Abemaciclib), administered in combination in patients affected by a defined type of advanced lung cancer (Stage IV Non-Small-Cell Lung Cancer)

• Register: EUCTR
• Last refreshed on: 19 March 2018
• Main ID: EUCTR2014-005042-21-ES
• Date of registration: 01/08/2016
• Prospective Registration: No
• Primary sponsor: Lilly S.A.
• Public title: A medical research evaluating the safety and efficacy of two new medicines (Necitumumab and Abemaciclib), administered in combination in patients affected by a defined type of advanced lung cancer (Stage IV Non-Small-Cell Lung Cancer)
• Scientific 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)
• Date of first enrolment: 29/07/2016
• Target sample size: 68
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005042-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Spain

Contacts

• Name: Clinical Trial Registry Office
• Affiliation: Lilly

• Name: Clinical Trial Registry Office
• Affiliation: Lilly

Key inclusion & exclusion criteria

Inclusion criteria:
Patients are eligible to be included in the study only if they meet all of the following criteria:
[1]Histologically or cytologically confirmed NSCLC
•Part A: NSCLC Stage IV (any type)
•Part B: NSCLC Stage IV (squamous and nonsquamous)
[2]Stage IV disease at the time of study entry (American Joint Committee on Cancer [AJCC] Staging Manual, 7th Edition [Edge et al. 2009])
[3]Measurable disease at the time of study entry as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (Eisenhauer et al. 2009)
[4]The patient 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 EGFR-TKI and ALK inhibitors is mandatory in patients whose tumor has EGFR-activating mutations or ALK translocations. Prior targeting agents and neoadjuvant/adjuvant therapies are permitted with the exception of CDK4/6-targeting agents or necitumumab.
[5]The patient has tumor tissue available for biomarker analyses. The sample can be either 12 serially paraffin-embedded unstained tissue slides or a paraffin embedded tissue block.
[6]The patient has given written informed consent prior to any study specific procedures. Written consent may also be provided by a legal representative.
[7]The patient is 18 years or older if required by local law or regulations.
[8]The patient has resolution to Grade =1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0, of all clinically significant toxic effects of prior chemotherapy, surgery, or radiotherapy (with the exception of alopecia).
[9]The patient has an Eastern Cooperative Oncology Group performance status score of 0-1.
[10]Have the following laboratory values:
•hematologic: absolute neutrophil count ?1.5 × 109/L, platelets ?100 × 109/L, and hemoglobin ?9 g/dL. T ransfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to Cycle 1 Day 1 are not allowed.
•Serum albumin =25 g/L
•hepatic: bilirubin ?1.5 × the upper limit of normal (ULN), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate transaminase (AST) ?3.0 times ULN. For patients with hepatic metastases, ALT and AST equaling =5.0 times ULN are acceptable.
•renal: serum creatinine ?1.2 x ULN or calculated creatinine clearance >50 mL/min (per the Cockcroft-Gault formula as defined in Attachment 5) for patients with creatinine >1.2 x ULN.

[11]are men who are sterile (including vasectomy confirmed by post-vasectomy semen analysis) or who agree to use a reliable method of birth control and to not donate sperm during the study (and for at least 12 weeks following the last dose of necitumumab and abemaciclib or country requirements, whichever is longer) OR
[12]are women who are either: (a) not of child-bearing potential due to surgical sterilization (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause; or (b) of child-bearing potential who have a negative serum pregnancy test within 14 days prior to study enrollment and agree to use a highly effective method of birth control during the study and for 6 months after the last dose of
Exclusion criteria:
Patients will be excluded from the study if they meet any of the following criteria:
[15]The patient is currently enrolled in a clinical trial involving an investigational product or non-approved use of a drug or device (other than the study treatment used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Prior treatment with CDK4/6-targeting agents or necitumumab is not permitted.
[16]The patient has undergone major surgery or received any investigational therapy in the 30-days prior to study enrollment.
[17]The patient has undergone chest irradiation within 4 weeks prior to receiving study treatment (except focal palliative irradiation, which is allowed up to 2 weeks prior to receiving study treatment).
[18]The patient has brain metastases that are symptomatic. (Patients who have completed radiotherapy for brain metastases at least 2 weeks prior to receiving study treatment, who are now non symptomatic or on stable dose of steroids or anticonvulsants during the 2 weeks prior to receiving study treatment, are eligible). Patients with asymptomatic brain metastases without need for treatment with steroids and who have not been treated with radiotherapy are eligible. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
[19]History of arterial or venous thromboembolism within 3 months prior to study enrollment. Patients 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.
[20]History or evidence of current clinically relevant coronary artery disease = Grade III by the Canadian Cardiovascular Society Angina Grading Scale or uncontrolled congestive heart failure of current > Class III as defined by the New York Heart Association.
[21]The patient has experienced myocardial infarction within 6 months prior to study enrollment.
[22]The patient 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).
[23]The patient has a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder, potentially precluding protocol compliance.
[24]The patient has a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
[25]The patient has any other serious uncontrolled medical disorders or psychological conditions that would, in the opinion of the investigator, limit the patient’s ability to complete the study or sign an informed consent document.
[26]The patient 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.
[27]The patient is pregnant or breastfeeding.
[28]The patient has a known history of drug abuse, that in the opinion of the investigator, may have an impact on the safety of the patient and/or limit the patient’s ability to complete th

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non Small Cell Lung Cancer
MedDRA version: 19.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Portrazza
Product Name: Necitumumab
Product Code: LY3012211
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Necitumumab
CAS Number: 906805-06-9
Other descriptive name: NECITUMUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 16-

Product Name: Abemaciclib
Product Code: LY2835219
Pharmaceutical Form: Capsule
INN or Proposed INN: Not available
CAS Number: 1231929-97-7
Other descriptive name: LY2835219
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: Part A: to determine the dose-limiting toxicity (DLT) of abemaciclib at doses up to 200 mg when combined with necitumumab 800 mg, in patients with Stage IV NSCLC as measured by the number of patients with a DLT in Cycle 1.

Part B: to evaluate the efficacy of necitumumab in combination with abemaciclib in terms of PFS rate at 3 months in patients with Stage IV NSCLC.

Primary end point(s): PART A: dose-limiting toxicity (DLT) of abemaciclib when combined with necitumumab 800 mg, as measured by the number of patients with a DLT in Cycle 1

PART B: The primary endpoint is Progression Free Survival Rate at 3 months as defined by RECIST 1.1 (Eisenhauer et al. 2009).

Secondary Objective: Part A:
•to investigate the safety profile as assessed by clinical and laboratory significant events of necitumumab in combination with abemaciclib
•to determine the overall response rate (ORR)
•to determine pharmacokinetics (PK) of necitumumab and abemaciclib
•to determine the immunogenicity of necitumumab
Part B:
To demonstrate the safety, efficacy and feasibility of necitumumab in combination with abemaciclib at the recommended dose by
•to determine PFS
•to determine ORR and disease control rate (DCR)
•to estimate OS
•to investigate the safety profile as assessed by clinical and laboratory significant events
•to determine pharmacokinetics (PK) of necitumumab and abemaciclib
•to determine the immunogenicity of necitumumab

Timepoint(s) of evaluation of this end point: PART A: cycle 1 of each cohort

PART B: approximately 5 month after enrollment completion

Secondary Outcome(s)

Secondary end point(s): PART A and Part B
Objective Response Rate (ORR): The objective response rate is the percentage of patients with a best response of CR or PR.
Immunogenicity: Incidence of anti-necitumumab antibodies will be tabulated.
Pharmacokinetics: Pharmacokinetic parameters of abemaciclib and necitumumab in Part A will be calculated using noncompartmental analysis (NCA) methodology. Summary level data for Part B will be presented as graphics and table listings.
Safety: Safety analyses will be performed for all patients enrolled in the study who receive any amount of study drug (necitumumab or abemaciclib).

PART B only
Progression Free Survival Rate (PFS): The time from the date of enrollment to the date of objective progression or the date of death due to any cause, whichever is earlier as defined by RECIST 1.1 (Eisenhauer et al. 2009)
Overall Survival (OS): OS duration is measured from the date of enrollment to the date of death from any cause.
Disease Control Rate (DCR): The proportion of patients in the analysis population who exhibit a SD or confirmed CR or PR relative to baseline during the study. Response is defined by RECIST 1.1 (Eisenhauer et al. 2009).

Timepoint(s) of evaluation of this end point: Safety:An interim safety analysis will be performed after the first 15 evaluable patients in the Part B portion of the trial have completed 2 cycles of study treatment (or otherwise discontinued study treatment). Patients with squamous and nonsquamous NSCLC who received the recommended abemaciclib dose for Part B in Part A will be taken into account for the safety interim analysis. The interim analysis will be conducted to permit evaluation of safety data by the sponsor.

All endpoints:approximately 5 month after enrollment completion

Secondary ID(s)

2014-005042-21-BE

I4X-MC-JFCU

Source(s) of Monetary Support

Eli Lilly and Company