A Study of IMC-RON8 in Advanced Solid Tumors

NCT01119456 | Completed Phase 1 Results

• 3 other identifiers: 13958CP21-0901I5D-IE-JRCA
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

Brief Summary

A dose escalation study to determine the maximum tolerated dose of IMC-RON8 in participants with solid tumors. Participants can either be dosed once a week, or once every other week.

Conditions

Cancer

Keywords

Tumors; Macrophage stimulating 1 receptor, human; RON protein; RON receptor protein tyrosine kinase

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of IMC-RON8

  The MTD was the previous dose level to that in which 2 of 6 participants experienced dose-limiting toxicities (DLTs). DLTs were defined as any of the following events: Grade 4 neutropenia lasting \>7 days; any Grade 3 or 4 neutropenia complicated by fever ≥38.5 degrees Celsius or infection, Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage; Grade 3 hepatic toxicity; or any Grade 3 or 4 nonhematologic toxicity (excluding alopecia, fatigue, anorexia, nausea, and vomiting that is controlled with antiemetics).

  Baseline through end of study treatment (up to 48 weeks)

Secondary Outcomes (5)

• Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8

  First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose

• PK: Area Under the Curve (AUC) of IMC-RON8

  First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose

• Immunogenicity of IMC-RON8

  Prior to first infusion through study completion (up to 52 weeks)

• Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8)

  Prior to first infusion through 1 hour post last infusion (end of study treatment, up to 48 weeks)

• Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors)

  Baseline to measured PD (up to 48 weeks)

Other Outcomes (1)

• Number of Participants Who Died

  Baseline through study completion (up to 52 weeks)

Study Arms (1)

IMC-RON8

EXPERIMENTAL

A monoclonal antibody to human macrophage-stimulating 1-receptor-8 (RON8).

Biological: IMC-RON8

Interventions

IMC-RON8 BIOLOGICAL

5 milligrams per kilogram (mg/kg) intravenously (IV) Once a week for each 4-week treatment cycle, for a total of four doses per cycle. The initial 4-week treatment cycle will be followed by a 2-week observation period. Cohort 1

Also known as: Narnatumab, LY3012219

IMC-RON8

Eligibility Criteria

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

You may qualify if:

• The participant has histologically-confirmed advanced primary or recurrent solid tumors that have not responded to standard therapy or for which no standard therapy is available
• The participant has measurable or non-measurable disease
• The participant has not received major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy within 28 days prior to the first dose of study therapy
• The participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-2
• The participant has adequate hematologic function
• The participant has adequate renal function as defined by serum creatinine ≤1.5 times the institutional upper limit of normal (ULN)
• The participant has a life expectancy \>3 months

You may not qualify if:

• The participant has received chemotherapy or therapeutic radiation therapy within 28 days prior to the first dose of study therapy
• The participant has ongoing toxicities of \>Grade 1 associated with any prior treatment
• The participant has a known sensitivity to monoclonal antibodies or other therapeutic agents, or to agents of similar biologic composition as IMC-RON8
• The participant has received treatment with any monoclonal antibodies within 6 weeks prior to first dose of study therapy
• The participant has received treatment with agents specifically targeting the RON ligand or receptor within 6 weeks prior to first dose of study therapy
• The participant has undergone a major surgical procedure, open biopsy, or experienced a significant traumatic injury within 28 days prior to the first dose of study therapy
• The participant has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia (well controlled atrial fibrillation is permitted), psychiatric illness/social situations, active bleeding, or any other serious uncontrolled medical disorders in the opinion of the investigator
• The participant has known or suspected brain or leptomeningeal metastases (participants with a history of brain metastases must have received definitive surgery or radiotherapy, be clinically stable, and may not be taking steroids; participants receiving anticonvulsants are eligible)
• The participant has a serious or nonhealing active wound, ulcer, or bone fracture
• The participant is currently using or has received a thrombolytic agent within 28 days prior to first dose of study therapy
• The participant is receiving full-dose warfarin (participants receiving low-dose warfarin to maintain the patency of permanent, indwelling intravenous catheters are eligible if the international normalized ratio is \<1.5)
• The participant is receiving intravenous heparin

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician

Indianapolis, Indiana, 46202, United States

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician

Detroit, Michigan, 48201, United States

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Neoplasms

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
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2010
• First Posted: May 7, 2010
• Study Start: May 1, 2010
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: February 15, 2019
• Results First Posted: February 15, 2019

Record last verified: 2018-10

Locations

US (3)