CancerPhase 1NCT01119456
A Study of IMC-RON8 in Advanced Solid Tumors
A Phase 1 study testing IMC-RON8 in people with Cancer, run by Eli Lilly and Company at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- IMC-RON8
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2010to Nov 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
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
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
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
About this study
Official 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
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
- Being tested
- IMC-RON8
- Keywords
- Tumors, Macrophage stimulating 1 receptor, human, RON protein, RON receptor protein tyrosine kinase
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMC-RON8Biological
Also called Narnatumab, LY3012219
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
IMC-RON8Biological
Also called Narnatumab, LY3012219
10 mg/kg 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 2
IMC-RON8Biological
Also called Narnatumab, LY3012219
15 mg/kg 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 3
IMC-RON8Biological
Also called Narnatumab, LY3012219
15 mg/kg IV
Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.
Cohort 4
IMC-RON8Biological
Also called Narnatumab, LY3012219
20 mg/kg IV
Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.
Cohort 5
IMC-RON8Biological
Also called Narnatumab, LY3012219
25 or 30 mg/kg IV
Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.
Cohort 6
IMC-RON8Biological
Also called Narnatumab, LY3012219
30, 35, or 40 mg/kg IV
Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.
Cohort 7
IMC-RON8Biological
Also called Narnatumab, LY3012219
20 or 25 mg/kg IV
Once every week for each 4-week treatment cycle, for a total of four doses per cycle.
Cohort 8
| Study group | Role | What they receive |
|---|---|---|
| IMC-RON8 | Experimental | A monoclonal antibody to human macrophage-stimulating 1-receptor-8 (RON8). Receives: Biological: IMC-RON8 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline through end of study treatment (up to 48 weeks)
Secondary outcomes (5)
Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8
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.
Measured: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
PK: Area Under the Curve (AUC) of IMC-RON8
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.
Measured: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
Immunogenicity of IMC-RON8
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.
Measured: Prior to first infusion through study completion (up to 52 weeks)
Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8)
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.
Measured: 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)
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.
Measured: Baseline to measured PD (up to 48 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2010 (estimated)
- Study startMay 2010
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01119456
- Sponsor's protocol ID
- 13958
- Other IDs
- CP21-0901, I5D-IE-JRCA
- Status last verified
- Oct 2018
- First submitted
- 6 May 2010
- Last updated
- 15 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01119456
- Acronym / sponsor ID
- 13958
- Conditions
- Cancer
- Keywords
- Tumors, Macrophage stimulating 1 receptor, human, RON protein, RON receptor protein tyrosine kinase
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- May 2010
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 7 May 2010 (estimated)
- Results
- Posted 15 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IMC-RON8 | Experimental | Biological: IMC-RON8A monoclonal antibody to human macrophage-stimulating 1-receptor-8 (RON8). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMC-RON8Also: Narnatumab, LY30122195 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 | Biological | IMC-RON8 |
| IMC-RON8Also: Narnatumab, LY301221910 mg/kg 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 2 | Biological | IMC-RON8 |
| IMC-RON8Also: Narnatumab, LY301221915 mg/kg 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 3 | Biological | IMC-RON8 |
| IMC-RON8Also: Narnatumab, LY301221915 mg/kg IV Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle. Cohort 4 | Biological | IMC-RON8 |
| IMC-RON8Also: Narnatumab, LY301221920 mg/kg IV Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle. Cohort 5 | Biological | IMC-RON8 |
| IMC-RON8Also: Narnatumab, LY301221925 or 30 mg/kg IV Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle. Cohort 6 | Biological | IMC-RON8 |
| IMC-RON8Also: Narnatumab, LY301221930, 35, or 40 mg/kg IV Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle. Cohort 7 | Biological | IMC-RON8 |
| IMC-RON8Also: Narnatumab, LY301221920 or 25 mg/kg IV Once every week for each 4-week treatment cycle, for a total of four doses per cycle. Cohort 8 | Biological | IMC-RON8 |
Primary outcome
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).
5 secondary outcomes
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
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
Immunogenicity of IMC-RON8
Time frame: Prior to first infusion through study completion (up to 52 weeks)
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IMC-RON8 in people with Cancer, run by Eli Lilly and Company at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of IMC-RON8 (time frame: Baseline through end of study treatment (up to 48 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2019.