Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Adenocarcinoma

Carcinoma, Hepatocellular

Carcinoma, Renal Cell

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Ramucirumab

Angiogenesis Inhibitors

Growth Inhibitors

Part A: Dose escalation (750mg, 2000mg) of Emibetuzumab administered intravenously (IV), on days 1 and 15 every 28 day cycle in combination with a fixed dose of 8mg/kg ramucirumab administered IV on Days 1 and 15 every 28 day cycle.

Part B: Recommended 750mg Emibetuzumab dose from Part A to be administered IV, on days 1 and 15 every 28 day cycle in combination with a fixed dose of 8mg/kg ramucirumab administered IV on Days 1 and 15 every 28 day cycle.

Emibetuzumab

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)

The purpose of this study is to find a recommended schedule and dose range for Emibetuzumab when given with ramucirumab that may be safely given to participants with cancer. In Part A of this study, escalating doses of Emibetuzumab will be given in combination with a fixed dose of ramucirumab to evaluate the safety of the combination. After a recommended schedule and dose range of Emibetuzumab and ramucirumab has been established, Part B of the study will confirm safety and to see how well certain tumors respond to the combination of study drugs. The average amount of time on study is expected to be about 6 months.

A Study of Emibetuzumab in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer

A Phase 1b/2 Study of Ramucirumab in Combination With LY2875358 in Patients With Advanced Cancer

DLT is defined as an adverse event during Cycle1 that is possibly, probably, or definitely related to treatment with Emibetuzumab in combination with fixed regimen of Ramucirumab \& fulfills any 1 of the following criterion using NCI CTCAE Version 4.03:

Grade 3 non-hematological toxicity. Exceptions will be made for:Nausea, vomiting, diarrhea, constipation, or skin rash that persists for ≤3 days following appropriate supportive care intervention. Grade 3 hypertension in which systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg persist \<7 days after intensified antihypertensive therapy is initiated.

Grade 4 hematological toxicity of ≥7 days duration.

≥Grade 3 thrombocytopenia with ≥Grade 2 bleeding.

Any febrile neutropenia.

Any other significant toxicity deemed by the primary investigator \& Lilly clinical research personnel to be dose-limiting (eg, any toxicity that is possibly related to the study medication that requires the withdrawal of participant from study Cycle1).

ORR is the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD 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 5mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Emibetuzumab.

DCR is the proportion of participants who exhibit a SD or confirmed CR or PR relative to baseline. 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 LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Progressive disease (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 5mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

PFS was defined as the time from the date of first dose of study drug until first observation of objective (radiographically documented) PD as defined by RECIST v1.1 or death from any cause, whichever comes first. PD 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.

Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) from time zero to tlast of Emibetuzumab.

Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab.

Participants were considered as treatment-emergent anti drug antibodies (TE ADA) positive if there is a ≥4-fold increase from baseline when ADAs were detected at baseline. If no ADAs were detected at baseline, TE ADA were defined as those with a titer 2 fold (1 dilution) greater than the minimum required dilution (MRD) of the screening assay (1:4 for anti-emibetuzumab antibodies).

Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Ramucirumab.

Participants were considered as treatment-emergent anti drug antibodies (TE ADA) positive if there is a ≥4-fold increase from baseline when ADAs were detected at baseline. If no ADAs were detected at baseline, TE ADA were defined as those with a titer 2 fold (1 dilution) greater than the minimum required dilution (MRD) of the screening assay (1:10 for anti-ramucirumab antibodies).

Eli Lilly and Company

All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.

Participants received 8 milligram per kilogram (mg/kg) Ramucirumab followed by 750 mg Emibetuzumab given as intravenous (IV) infusion on days 1 and 15 of 28 days cycle.

Part A - 750 mg Emibetuzumab

Participants received 8 mg/kg Ramucirumab followed by 2000 mg Emibetuzumab given as intravenous (IV) infusion on days 1 and 15 of 28 days cycle.

Part A - 2000 mg Emibetuzumab

Participants received 8 mg/kg Ramucirumab followed by 750mg Emibetuzumab given as intravenous (IV) infusion on days 1 and 15 of 28 days cycle.

Part B - Gastric

Participants received 8 mg/kg Ramucirumab followed by 750 mg Emibetuzumab given as intravenous (IV) infusion on days 1 and 15 of 28 days cycle.

Part B - HCC

Part B - RCC

Part B - NSCLC

Total

Age, Continuous

Sex: Female, Male

All participants with baseline ethnicity data.

Ethnicity (NIH/OMB)

All randomized participants with baseline race data.

Race (NIH/OMB)

United States

Region of Enrollment

Chief Medical Officer

All participants who received at least one dose of Emibetuzumab in Part A \& Part B.

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

All participants who received at least one dose of Emibetuzumab in Part B.

Part B: Percentage of Participants Who Exhibit Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]

All Parts - 750 mg Emibetuzumab

All Parts - 2000 mg Emibetuzumab

All participants who received at least one dose of Emibetuzumab and had evaluable PK samples in Part A \& Part B.

Per protocol analysis was performed per each dose irrespective of the study parts.

Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Emibetuzumab

Part B: Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR) (Disease Control Rate [DCR])

All participants who received at least one dose of Emibetuzumab in part B. Censored participants in Part B- Gastric = 4; Part B - HCC = 15; Part B - RCC = 7; Part - B NSCLC = 4;

Part B: Progression Free Survival (PFS)

All participants who received at least one dose of Emibetuzumab and had evaluable PK samples in Part A \& Part B.

Per protocol, analysis was performed per each dose irrespective of study parts.

Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) From Time Zero to Tlast of Emibetuzumab

All Parts - 750mg

All Parts - 2000mg

Noncompartmental PK parameters were not generated for Ramucirumab due to inadequate PK sampling.

Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab

All participants who received at least one dose of Emibetuzumab and had evaluable immunogenicity samples.

Number of Participants With Treatment Emergent Anti-Emibetuzumab Antibodies

Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Ramucirumab

All participants who received at least one dose of ramucirumab and had evaluable immunogenicity samples.

Number of Participants With Treatment Emergent Anti-Ramucirumab Antibodies

Overall Study

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Amino Acids

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

750 milligram (mg) Emibetuzumab flat dose given as a 1.5 hour intravenous (IV) infusion on Days 1 and 15 of a 28-day cycle and Erlotinib 150 mg given orally once daily on a 28-day cycle.

750 mg Emibetuzumab flat dose given as a 1.5-hour IV infusion on Days 1 and 15 of a 28-day cycle.

Erlotinib

The primary purpose of this study is to evaluate the efficacy of the study drug known as LY2875358, administered alone or in combination with a second drug named Erlotinib, in participants affected by a defined type of lung cancer (MET biomarker diagnostic positive Non-Small-Cell Lung Cancer) that experienced a disease progression during the most recent treatment with Erlotinib.

A Study of Emibetuzumab in Non Small Cell Lung Cancer (NSCLC) Participants

A Randomized, Open-Label Phase 2 Study Evaluating LY2875358 Plus Erlotinib and LY2875358 Monotherapy in MET Diagnostic Positive NSCLC Patients With Acquired Resistance to Erlotinib

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

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.

PFS defined as date of randomization until the date of objectively determined progression defined by Response Evaluation Criteria in Solid Tumors criteria or death from any cause, whichever is first.

Progressive disease (PD) defined as ≥20% increase in sum of diameter of target lesion with the sum demonstrating an increase of ≥5 mm; appearance of ≥1 new lesions or unequivocal progression of non- target lesions. Participants with no baseline disease assessment were censored at randomization date, regardless of whether or not objectively determined PD or death was observed; participants not known to have died or to have objective progression as of data inclusion cutoff were censored at last post baseline radiological assessment date or randomization date, if there was no post baseline radiological assessment.

Zero participants analyzed. CTS data was not collected for analysis due to N=0 CR and N=3 PR.

Participants achieved disease control if they had a best overall response of PR, CR or SD. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal \[ULN\]); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. The percentage of participants who achieved disease control equals (number of participants with CR, PR, or SD)/(number of participants assessed)\*100.

Zero participants analyzed. Duration of Response for CR and PR data was not collected for analysis due to N=0 CR and N=3 PR.

OS was defined as duration from the date of study enrollment to the date of death from any cause. Participants not known to have died as of the data inclusion cut-off date were censored at the date of last contact. The last contact for participants in post-discontinuation was the last date participant was known to be alive.

EORTC QLQ-C30 v3.0 is a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms.

The EORTC lung module QLQ-LC13 comprises 13 items consisting of one multi-item scale to assess dyspnea and a series of single-item measures assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. The higher scores represent a greater degree of symptoms.

The EQ-5D is a generic, multidimensional, health status instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). A negative change indicated a worsening of the participant's health status.

Additionally, participants will indicate their current health status by marking on a continuum ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).

AUC(0-tlast) = area under the concentration versus time curve from time zero through the last quantifiable sample.

Arm A: Emibetuzumab Plus Erlotinib

Arm B: Emibetuzumab

750 milligram (mg) Emibetuzumab (LY2875358) flat dose given as a 1.5 hour intravenous (IV) infusion on Days 1 and 15 of a 28-day cycle and Erlotinib 150 mg given orally once daily on a 28-day cycle.

Netherlands

Belgium

South Korea

Italy

United Kingdom

Israel

France

Germany

Spain

ECOG 0

ECOG 1

ECOG 2

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) classifies participants according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death). 0 - Fully Active. 1 - Ambulatory, Restricted Strenuous Activity. 2 - Ambulatory, No Work Activities. 3 - Partially Confined to Bed, Limited Self Care. 4 - Completely Disabled. 5 - Death.

ECOG Performance Status

Lung Adenocarcinoma

Squamous Cell Carcinoma

Large Cell Carcinoma

Other Subtypes of Lung Cancer

Pathological Diagnosis

All randomized participants who received at least one dose of study drug.

Participants in the Emibetuzumab + Erlotinib treatment arm with MET-High expression status based on their post-erlotinib progression NSCLC tumor sample.

MET-High Analysis Population (Emibetuzumab + Erlotinib)

Participants in the Emibetuzumab treatment arm with MET-High expression status based on their post- erlotinib progression NSCLC tumor sample.

MET-High Analysis Population (Emibetuzumab)

All participants who are MET diagnostic positive based on the results of their post-erlotinib progression tumor sample and resistance to erlotinib.

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])

Progression Free Survival (PFS)

Time to Progressive Disease

Arm B: LY2875358

Zero participants analyzed.CTS data was not collected for analysis due to N=0 CR and N=3 PR.

Change in Tumor Size (CTS)

Secondary: Percentage of Participants Who Achieved Best Overall Disease Response of CR, PR or Stable Disease (SD) [Disease Control Rate (DCR)]

Duration of Response (DoR)

Overall Survival (OS)

Physical

Role

Emotional

Cognitive

Social

Fatigue

Nausea/vomiting

Pain

Dyspnea

Insomnia

Appetite Loss

Constipation

Diarrhea

Finance

Participants with MET-High expression status based on their post-erlotinib progression NSCLC tumor sample.

MET-High Analysis Population

All randomized participants with EORTC QLQ-C30 values at baseline.

Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires C30 (QLQ-C30)

Coughing

Hemoptysis

Sore Mouth

Dysphagia

Peripheral Neuropathy

Alopecia

Pain in Chest

Pain in Shoulder or Arm

Pain in Other Parts

All randomized participants with EORTC QLQ-LC13 values at baseline.

Change From Baseline in EORTC Quality of Life Questionnaires Lung Cancer 13 (QLQ-LC13)

Index Score

Visual Analog Scale

All randomized participants with EQ-5D values at baseline.

Change From Baseline in EuroQol 5-Dimensional Scale (EQ-5D)

All participants who received Emibetuzumab on Cycle 1, Day 1, and contributed samples for analysis.

Pharmacokinetics (PK): Area Under the Concentration (AUC) of Emibetuzumab

All participants who received at least one dose of study drug and have sufficient Anti-Emibetuzumab Antibody sample for the analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Emibetuzumab in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer	NCT02082210	Advanced Cancer Gastric Adenoca... Gastroesophagea... Hepatocellular ... Renal Cell Carc... Non-Small Cell ...	Emibetuzumab Ramucirumab	18 Years -	Eli Lilly and Company
A Study of Emibetuzumab in Non Small Cell Lung Cancer (NSCLC) Participants	NCT01900652	Carcinoma, Non-...	Emibetuzumab Erlotinib	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for emibetuzumab

Every month we try and update this database with for emibetuzumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.