A Drug-Interaction Study of Necitumumab (IMC-11F8) in Combination With Gemcitabine-Cisplatin

Study Overview
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Brief Summary
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The purpose of this study is to investigate the pharmacokinetics (PK) of necitumumab in combination with gemcitabine-cisplatin in participants with advanced malignant solid tumors and to assess the potential for drug-drug interactions between necitumumab and gemcitabine-cisplatin.

Official Title
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An Open-Label, Non-controlled, Non-randomized Sequential Design, Drug-Interaction Study of Necitumumab (IMC-11F8) in Combination With Gemcitabine-Cisplatin in Patients With Advanced Solid Cancers

Conditions
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Malignant Solid Tumor

Intervention / Treatment
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* Biological: Necitumumab
* Drug: Gemcitabine
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have documented advanced or metastatic malignant solid tumors (except for colorectal tumors with KRAS mutation) that are resistant to standard therapy or for which no standard therapy is available May have measurable or non-measurable disease Have resolution to Grade 0 or 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE 4.0) of all clinically significant toxic effects (other than alopecia) of prior chemotherapy, surgery, radiotherapy, or hormonal therapy Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1 Have adequate hepatic, hematologic and renal function If female, are surgically sterile, postmenopausal, or agree to be compliant with a highly effective contraceptive method during and for 6 months after the treatment period. If male, are surgically sterile or agree to be compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period Female participants of childbearing potential have a negative serum pregnancy test within 7 days prior to the first dose of study therapy Exclusion Criteria: Have received a systemic anticancer agent (including EGFR tyrosine kinase inhibitors) or device within 28 days prior to first dose of study therapy The most recent anticancer therapy received by the participant included either gemcitabine or cisplatin (or both) Have received radiotherapy within 14 days prior to first dose of study therapy Have received cytotoxic chemotherapy within 21 days prior to first dose of study therapy Are receiving concurrent treatment with another anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiation therapy, chemoembolization, or targeted therapy Are considered surgical candidates (with resectable disease) Have brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants Have narrowing of or blockage in large veins Have coronary artery disease or uncontrolled congestive heart failure Have uncontrolled angina pectoris, or experienced myocardial infarction within 6 months prior to first dose of study therapy Have an ongoing or active infection (requiring treatment), including active tuberculosis or known infection with the human immunodeficiency virus Have a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder Have known drug or alcohol abuse If female, are pregnant or breastfeeding Have had major surgery within 28 days prior to first dose of study medication or subcutaneous venous access device implantation within 7 days prior to first dose of study therapy Are currently enrolled in, or discontinued within the 30 days prior to first dose of study therapy from a clinical trial involving an investigational product or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Necitumumab, Gemcitabine and Cisplatin<br>The study will be conducted in two sequential periods: a 3-week PK run-in participants will be treated sequentially with single doses of cisplatin, gemcitabine, and necitumumab. Cycle 1 will begin immediately following the PK run-in period. | Biological: Necitumumab<br>* PK Run-In Period: Necitumumab administered on Day 3 of the 3-week PK run-in period as an intravenous (I.V.) infusion at an absolute dose of 800 mg Treatment Cycles: Necitumumab administered on Days 1 and 8 of every 3-week cycle as an intravenous (I.V.) infusion at an absolute dose of 800 mg Participants in Cohort 1 will receive necitumumab Process C drug product and participants in Cohort 2 will receive necitumumab Process D drug product<br>* Other names: LY3012211;Drug: Gemcitabine<br>* PK Run-In Period: Gemcitabine administered on Day 1 of the 3-week PK run-in period as an I.V. infusion at a dose of 1250 milligram per square meter (mg/m2) Treatment Cycles: Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an I.V. infusion at a dose of 1250 mg/m2<br>* Other names: LY188011;Drug: Cisplatin<br>* PK Run-In Period: Cisplatin administered on Day 1 of the 3-week PK run-in period as an I.V. infusion at a dose of 75 mg/m2 Treatment Cycles: Cisplatin administered on Day 1 of every 3-week cycle as an I.V. infusion at a dose of 75 mg/m2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab |  | Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 Hour (h) Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion | 
| PK: Dose-Normalized Cmax of Gemcitabine |  | Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion | 
| PK: Dose-Normalized Cmax of Cisplatin |  | Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion | 
| PK: Area Under Concentration-Time Curve From Zero to Time 168 (AUC[-168]) of Necitumumab |  | Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion | 
| PK: Dose-Normalized AUC(0-24) of Gemcitabine |  | Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion | 
| PK: Dose-Normalized AUC(0-5) of Cisplatin |  | Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion | 
| PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, (AUC[0-∞]) of Necitumumab |  | Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1 Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion | 
| PK: Dose Normalized AUC(0-∞) of Gemcitabine |  | Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Anti-Necitumumab Antibodies | A participant was considered to have an anti-necitumumab antibody response if anti-drug antibodies (ADA) were confirmed positive. Treatment emergent antibodies were defined as any anti-necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer. | Baseline through, 30-Day Follow-Up | 
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) (Antitumor Activity of Necitumumab in Combination With Gemcitabine-cisplatin Chemotherapy) | ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, CR was defined as the disappearance of all target and non-target lesions; PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD. Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) * 100. | Baseline to Measured Progressive Disease (Up to 14 Months) | 
| PK: Cmax of Necitumumab After Administration of Process C and Process D Drug Product |  | Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion | 
| PK: AUC(0-∞) of Necitumumab After Administration of Process C and Process D Drug Product |  | Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Malignant Solid Tumors, Solid Cancers, Non-small Cell Lung Cancer, NSCLC, Breast Cancer