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OpenTrials
Completed

NCT Number: NCT01119456

A Study of IMC-RON8 in Advanced Solid Tumors

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.

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Key information

Conditions

Cancer Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary 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, Indianapolis, Indiana, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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

Other names: Narnatumab, LY3012219

Primary outcomes

  1. Maximum Tolerated Dose (MTD) of IMC-RON8

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

    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).

Secondary outcomes

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

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

    The Cmax of IMC-RON8 following the first and multiple IV infusions (the fourth infusion for the qw treatment regimen and the fifth infusion for the q2w treatment regimen) is reported. PK samples were collected per protocol and individual sampling times varied depending on the treatment arm and infusion (first or multiple). The geometric mean and geometric coefficient of variation (%CV) were calculated for treatment arms that had ≥3 participants who had evaluable PK samples for Cmax.

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

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

    The AUC from time 0 to the last quantifiable concentration [AUC(0-tlast)] of IMC-RON8 following the first IV infusion is reported along with the AUC for 1 dosing interval (AUC tau). Tau = fourth infusion through 168 hours post infusion for the qw regimen and the fifth infusion through 336 hours post infusion for the q2w regimen. PK samples were collected per protocol and individual sampling times varied depending on the treatment arm and infusion (first or multiple). The geometric mean and geometric coefficient of variation (%CV) were calculated for treatment arms that had ≥3 participants who had evaluable PK samples for AUC(0-tlast) or AUC tau.

  3. Immunogenicity of IMC-RON8

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

    An immunogenicity assay for IMC-RON8 was not developed due to the decision to not further develop IMC-RON8 based on preliminary results of this study.

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

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

    The expression of RON8 was measured in cell membrane/cytoplasm by immunohistochemistry (IHC) methods that incorporated both intensity and distribution of staining. The H-Score was calculated by summing the percentage of cell staining at each intensity multiplied by the weighted intensity of staining: 0 (no staining), 1+ (weak staining), 2+ (medium staining), 3+ (strongest staining). H-Scores could range from a minimum score of 0 to a maximum score of 300; the maximum score indicated the strongest expression. Pharmacodynamic samples were collected per protocol and individual sampling times varied depending on the treatment group.

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

    Time frame: Baseline to measured PD (up to 48 weeks)

    Response was defined using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST, v 1.1) criteria. CR was the disappearance of all target and nontarget lesions; and any pathological lymph node (whether target or nontarget) must have had a reduction in short axis to <10 millimeters (mm) and normalization of tumor marker level of nontarget lesions. The disappearance of any intratumoral arterial enhancement in all target lesions was also required. PR was having at least a 30% decrease in sum of longest diameter of target lesions. PD was having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir and the unequivocal progression of existing nontarget lesions. SD was small changes that did not meet the above criteria.

Other outcomes

  1. Number of Participants Who Died

    Time frame: Baseline through study completion (up to 52 weeks)

    The number of participants who died is reported by cause of death.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

Phase 1 Study of the Anti-Ron Receptor Monoclonal Antibody IMC-RON8 in Patients With Advanced Solid Tumors Who No Longer Respond to Standard Therapy or for Whom No Standard Therapy is Available

Important dates

Study start
2010
Primary completion
2013
Study completion
2013
First posted
May 7, 2010
Registry last updated
Feb 15, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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