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.

Spots Global Cancer Trial Database for A Study of Emibetuzumab in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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