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

NCT02082210 | Completed Phase 1 Results

• 2 other identifiers: 15246I4C-MC-JTBF
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Advanced Cancer; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Hepatocellular Cancer; Renal Cell Carcinoma; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

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

  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).

  Baseline through Cycle 1 (28 day cycle)

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

  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.

  Baseline through Measured Progressive Disease or Death (Up to 17 months)

Secondary Outcomes (8)

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

  Cycle 1: Day1 Predose, End of infusion, 3 Hours (h), 5h, 8h, 21h, 168h, 334h, 335h and 336h Post dose

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

  Baseline through Measured Progressive Disease (Up to 17 months)

• Part B: Progression Free Survival (PFS)

  Baseline to Measured Progressive Disease or Death (Up to 17 Months)

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

  Cycle 1: Day1 Predose, End of infusion, 3 Hours (h), 5h, 8h, 21h, 168h, 334h, 335h and 336h Post dose

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

  Cycle 1: Day1 Predose, End of infusion, 3 Hours (h), 5h, 8h, 21h, 168h and 336h Post dose

Study Arms (2)

Emibetuzumab + Ramucirumab (Part A)

EXPERIMENTAL

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.

Drug: Emibetuzumab; Drug: Ramucirumab

Emibetuzumab + Ramucirumab (Part B)

EXPERIMENTAL

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.

Drug: Emibetuzumab; Drug: Ramucirumab

Interventions

Emibetuzumab DRUG

Administered Intravenously (IV)

Also known as: LY2875358

Emibetuzumab + Ramucirumab (Part A); Emibetuzumab + Ramucirumab (Part B)

Ramucirumab DRUG

Administered Intravenously (IV)

Also known as: LY3009806, IMC-1121B

Emibetuzumab + Ramucirumab (Part A); Emibetuzumab + Ramucirumab (Part B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histological or cytological confirmed diagnosis of the following tumor types that is advanced and/or metastatic cancer and must be, in the judgment of the investigator, an appropriate participant for experimental therapy
• Part A: Any type of solid tumor ("all comer")
• Part B1: Gastric or Gastroesophageal Junction (GEJ) adenocarcinoma
• Part B2: Hepatocellular cancer (excluding fibrolamellar carcinoma)
• Part B3: Renal cell carcinoma (any histology)
• Part B4: Non-small cell lung cancer (squamous or non-squamous)
• Have at least 1 measurable lesion outside of the central nervous system (CNS) whose presence is assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Availability of a tumor sample taken after progression on the most recent line of systemic tumor therapy or willing to undergo a tumor biopsy pre-study treatment.
• Have a performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale in Part A and ≤ 1 on the ECOG scale in Part B.
• Have adequate organ function.
• Routine urinalysis showing ≤1+ protein or protein/creatinine ratio \<0.5. For proteinuria ≥2+ or urine protein/creatinine ratio ≥0.5, 24-hour urine must be collected and the level must be \<1 gram of protein in 24 hours for subject enrollment.
• Have discontinued all previous cancer therapies and any agents that have not received regulatory approval for any indication, for at least 21 days or 5 halflives prior to study enrollment, whichever is shorter, and recovered from the acute effects for therapy.
• Have an estimated life expectancy, in the judgment of the investigator, that will permit the participant to complete 8 weeks (2 cycles) of treatment.
• Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and for at least 3 months following the last dose of study drug. Females with childbearing potential must have had a negative serum pregnancy test 7 days before the first dose of study drug and must not be breast-feeding.

You may not qualify if:

• Have serious pre-existing medical conditions (at the discretion of the investigator, such as severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with study participation).
• Have a history of hypertensive crisis or hypertensive encephalopathy or current poorly controlled hypertension despite standard medical management.
• Participant has experienced any arterial thromboembolic event (ATE), including myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack, within 6 months prior to receiving study drugs.
• Have a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolic event during the 3 months prior to receiving study drugs.
• Are receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or similar agents. Participants receiving prophylactic, low-dose anticoagulation therapy are eligible provided that they are on low-molecular weight heparin or oral factor Xa inhibitors.
• The participant is receiving chronic therapy with nonsteroidal anti-inflammatory drugs or other antiplatelet agents. Aspirin use at doses up to 325 mg/day is permitted.
• Have significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to receiving study drugs.
• Have a history of GI perforation and/or fistulae within 6 months prior to receiving study drugs.
• Have congestive heart failure (CHF) New York Heart Association class ≥3 or symptomatic or poorly controlled cardiac arrhythmia.
• Have undergone major surgery within 28 days prior to receiving study drugs.
• Have a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to receiving study drugs.
• Have a known active fungal, bacterial, and/or known viral infection. Hepatocellular cancer participants with chronic viral (B or C) hepatitis are eligible if they retain adequate liver function.
• Have liver cirrhosis with a Child-Pugh Stage of B or C.
• Have symptomatic CNS malignancy (with the exception of medulloblastoma) or metastasis.
• Have corrected QT (QTc) interval of \>470 milliseconds on screening electrocardiogram (ECG).

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114-3117, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Related Links

• Click here for more information about this study: A Study of LY2875358 in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung

Interventions

emibetuzumab; Ramucirumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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 DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2014
• First Posted: March 10, 2014
• Study Start: March 7, 2014
• Primary Completion: December 5, 2017
• Study Completion: January 24, 2018
• Last Updated: December 19, 2020
• Results First Posted: December 19, 2020

Record last verified: 2018-03

Locations

US (4)