Cancer
Conditions
Keywords
Tumors, Macrophage stimulating 1 receptor, human, RON protein, RON receptor protein tyrosine kinase
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.
Interventions
BIOLOGICALIMC-RON8
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
Sponsors
Eli Lilly and Company
Study design
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of IMC-RON8 | 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | 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. |
| PK: Area Under the Curve (AUC) of IMC-RON8 | 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. |
| Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | 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. |
| Immunogenicity of IMC-RON8 | 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. |
| 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) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Died | Baseline through study completion (up to 52 weeks) | The number of participants who died is reported by cause of death. |
Countries
United States
Participant flow
Pre-assignment details
In this dose escalation study, a completed participant was either a participant who completed the initial 4-week treatment cycle (and 2-weeks of observation for specified treatment arms) or one who discontinued therapy, during the same time period, for a narnatumab (IMC-RON8)-related toxicity.
Participants by arm
| Arm | Count |
|---|---|
| IMC-RON8 (5 mg/kg qw) IMC-RON8: 5 mg/kg IMC-RON8 administered IV qw for a total of 4 doses per cycle. The initial 4-week treatment cycle was followed by a 2-week observation period. Following the first 6-week tumor assessment, participants who responded to treatment (CR, PR, or SD) could continue treatment (same dose and frequency with no rest period) until PD, toxicity, or other withdrawal criteria were met. | 7 |
| IMC-RON8 (10 mg/kg qw) IMC-RON8: 10 mg/kg IMC-RON8 administered IV qw for a total of 4 doses per cycle.
The initial 4-week treatment cycle was followed by a 2-week observation period. Following the first 6-week tumor assessment, participants who responded to treatment (CR, PR, or SD) could continue treatment (same dose and frequency with no rest period) until PD, toxicity, or other withdrawal criteria were met. | 3 |
| IMC-RON8 (15 mg/kg qw) IMC-RON8: 15 mg/kg IMC-RON8 administered IV qw for a total of 4 doses per cycle.
The initial 4-week treatment cycle was followed by a 2-week observation period. Following the first 6-week tumor assessment, participants who responded to treatment (CR, PR, or SD) could continue treatment (same dose and frequency with no rest period) until PD, toxicity, or other withdrawal criteria were met. | 3 |
| IMC-RON8 (15 mg/kg q2w) IMC-RON8: 15 mg/kg IMC-RON8 administered IV q2w for a total of 2 doses per cycle.
Following the first 8-week tumor assessment, participants who responded to treatment (CR, PR, or SD) could continue treatment (same dose and frequency with no rest period) until PD, toxicity, or other withdrawal criteria were met. | 4 |
| IMC-RON8 (20 mg/kg q2w IMC-RON8: 20 mg/kg IMC-RON8 administered IV q2w for a total of 2 doses per cycle.
Following the first 8-week tumor assessment, participants who responded to treatment (CR, PR, or SD) could continue treatment (same dose and frequency with no rest period) until PD, toxicity, or other withdrawal criteria were met. | 3 |
| IMC-RON8 (30 mg/kg q2w) IMC-RON8: 30 mg/kg IMC-RON8 administered IV q2w for a total of 2 doses per cycle.
Following the first 8-week tumor assessment, participants who responded to treatment (CR, PR, or SD) could continue treatment (same dose and frequency with no rest period) until PD, toxicity, or other withdrawal criteria were met. | 3 |
| IMC-RON8 (40 mg/kg q2w) IMC-RON8: 40 mg/kg IMC-RON8 administered IV q2w for a total of 2 doses per cycle.
Following the first 8-week tumor assessment, participants who responded to treatment (CR, PR, or SD) could continue treatment (same dose and frequency with no rest period) until PD, toxicity, or other withdrawal criteria were met. | 3 |
| IMC-RON8 (20 mg/kg qw) IMC-RON8: 20 mg/kg IMC-RON8 administered IV qw for a total of 4 doses per cycle.
Participants continued treatment (same dose and frequency with no rest period) until PD, toxicity, or other withdrawal criteria were met. | 13 |
| Total | 39 |
Baseline characteristics
| Characteristic | IMC-RON8 (5 mg/kg qw) | IMC-RON8 (10 mg/kg qw) | IMC-RON8 (15 mg/kg qw) | IMC-RON8 (15 mg/kg q2w) | IMC-RON8 (20 mg/kg q2w | IMC-RON8 (30 mg/kg q2w) | IMC-RON8 (40 mg/kg q2w) | IMC-RON8 (20 mg/kg qw) | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 17.2 | 66.0 years STANDARD_DEVIATION 2 | 65.3 years STANDARD_DEVIATION 9.8 | 70.5 years STANDARD_DEVIATION 9.1 | 57.7 years STANDARD_DEVIATION 9.1 | 38.0 years STANDARD_DEVIATION 13.1 | 67.3 years STANDARD_DEVIATION 6 | 58.7 years STANDARD_DEVIATION 11.6 | 59.2 years STANDARD_DEVIATION 13.5 |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized Other | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 7 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 2 participants | 9 participants | 33 participants |
| Region of Enrollment United States | 7 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 13 Participants | 39 Participants |
| Sex: Female, Male Female | 5 Participants | 0 Participants | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 17 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 10 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 7 | 3 / 3 | 3 / 3 | 11 / 13 | 4 / 4 | 3 / 3 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 3 / 7 | 1 / 3 | 0 / 3 | 6 / 13 | 2 / 4 | 2 / 3 | 1 / 3 | 1 / 3 |
Outcome results
Primary
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).
Time frame: Baseline through end of study treatment (up to 48 weeks)
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMC-RON8 | Maximum Tolerated Dose (MTD) of IMC-RON8 | NA mg/kg |
Secondary
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.
Time frame: Baseline to measured PD (up to 48 weeks)
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IMC-RON8 | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | SD | 1 Participants |
| IMC-RON8 | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | Unknown | 2 Participants |
| IMC-RON8 | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | PD | 4 Participants |
| IMC-RON8 (10 mg/kg qw) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | Unknown | 0 Participants |
| IMC-RON8 (10 mg/kg qw) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | PD | 1 Participants |
| IMC-RON8 (10 mg/kg qw) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | SD | 2 Participants |
| IMC-RON8 (15 mg/kg qw) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | Unknown | 0 Participants |
| IMC-RON8 (15 mg/kg qw) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | SD | 0 Participants |
| IMC-RON8 (15 mg/kg qw) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | PD | 3 Participants |
| IMC-RON8 (20 mg/kg qw) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | SD | 3 Participants |
| IMC-RON8 (20 mg/kg qw) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | PD | 0 Participants |
| IMC-RON8 (20 mg/kg qw) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | Unknown | 1 Participants |
| IMC-RON8 (15 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | PD | 2 Participants |
| IMC-RON8 (15 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | SD | 0 Participants |
| IMC-RON8 (15 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | Unknown | 1 Participants |
| IMC-RON8 (20 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | PD | 2 Participants |
| IMC-RON8 (20 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | SD | 1 Participants |
| IMC-RON8 (20 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | Unknown | 0 Participants |
| IMC-RON8 (30 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | PD | 1 Participants |
| IMC-RON8 (30 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | SD | 2 Participants |
| IMC-RON8 (30 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | Unknown | 0 Participants |
| IMC-RON8 (40 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | SD | 2 Participants |
| IMC-RON8 (40 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | PD | 8 Participants |
| IMC-RON8 (40 mg/kg q2w) | Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors) | Unknown | 3 Participants |
Secondary
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.
Time frame: Prior to first infusion through study completion (up to 52 weeks)
Population: Zero participants analyzed. Immunogenicity data were not collected.
Secondary
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.
Time frame: Prior to first infusion through 1 hour post last infusion (end of study treatment, up to 48 weeks)
Population: Participants who received at least 1 dose of study drug and had tumor tissue samples.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IMC-RON8 | Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8) | 80 units on a scale |
| IMC-RON8 (10 mg/kg qw) | Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8) | 45 units on a scale |
| IMC-RON8 (15 mg/kg qw) | Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8) | 60 units on a scale |
| IMC-RON8 (20 mg/kg qw) | Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8) | 95 units on a scale |
| IMC-RON8 (15 mg/kg q2w) | Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8) | 133 units on a scale |
| IMC-RON8 (20 mg/kg q2w) | Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8) | 40 units on a scale |
| IMC-RON8 (30 mg/kg q2w) | Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8) | 40 units on a scale |
| IMC-RON8 (40 mg/kg q2w) | Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8) | 120 units on a scale |
Secondary
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.
Time frame: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
Population: Participants who received a first and/or fourth or fifth dose of study drug and had evaluable PK samples for Cmax. No participant was analyzed for the geometric mean (%CV) of Cmax after multiple infusions in the 15, 20, 30, and 40 q2w treatment arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| IMC-RON8 | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | First infusion | 111 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 31 |
| IMC-RON8 | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | Multiple infusions | 139 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 50 |
| IMC-RON8 (10 mg/kg qw) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | Multiple infusions | 263 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 17 |
| IMC-RON8 (10 mg/kg qw) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | First infusion | 183 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 24 |
| IMC-RON8 (15 mg/kg qw) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | Multiple infusions | 452 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 29 |
| IMC-RON8 (15 mg/kg qw) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | First infusion | 369 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 20 |
| IMC-RON8 (20 mg/kg qw) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | First infusion | 437 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 20 |
| IMC-RON8 (20 mg/kg qw) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | Multiple infusions | 518 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 25 |
| IMC-RON8 (15 mg/kg q2w) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | First infusion | 379 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 17 |
| IMC-RON8 (15 mg/kg q2w) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | Multiple infusions | NA micrograms per milliliter (mcg/mL) | — |
| IMC-RON8 (20 mg/kg q2w) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | First infusion | 506 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 39 |
| IMC-RON8 (30 mg/kg q2w) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | First infusion | 581 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 7 |
| IMC-RON8 (40 mg/kg q2w) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | Multiple infusions | NA micrograms per milliliter (mcg/mL) | — |
| IMC-RON8 (40 mg/kg q2w) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8 | First infusion | 706 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 24 |
Secondary
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.
Time frame: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
Population: Participants who received a first and/or fourth or fifth dose of study drug and had evaluable PK samples for AUC(0-tlast) or AUC tau. No participant was analyzed for the geometric mean (%CV) of AUC tau in the 15, 20, 30, and 40 q2w treatment arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| IMC-RON8 | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC(0-tlast) | 8320 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 63 |
| IMC-RON8 | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC tau | 10400 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 87 |
| IMC-RON8 (10 mg/kg qw) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC(0-tlast) | 12500 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 14 |
| IMC-RON8 (10 mg/kg qw) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC tau | 19400 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 11 |
| IMC-RON8 (15 mg/kg qw) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC tau | 31500 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 51 |
| IMC-RON8 (15 mg/kg qw) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC(0-tlast) | 23800 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 37 |
| IMC-RON8 (20 mg/kg qw) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC tau | 29900 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 47 |
| IMC-RON8 (20 mg/kg qw) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC(0-tlast) | 29000 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 30 |
| IMC-RON8 (15 mg/kg q2w) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC tau | NA micrograms*hour/milliliter (mcg*h/mL) | — |
| IMC-RON8 (15 mg/kg q2w) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC(0-tlast) | 35600 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 22 |
| IMC-RON8 (20 mg/kg q2w) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC(0-tlast) | 40500 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 87 |
| IMC-RON8 (30 mg/kg q2w) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC(0-tlast) | 56900 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 34 |
| IMC-RON8 (40 mg/kg q2w) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC(0-tlast) | 70200 micrograms*hour/milliliter (mcg*h/mL) | Geometric Coefficient of Variation 25 |
| IMC-RON8 (40 mg/kg q2w) | PK: Area Under the Curve (AUC) of IMC-RON8 | AUC tau | NA micrograms*hour/milliliter (mcg*h/mL) | — |
Other Pre-specified
Number of Participants Who Died
The number of participants who died is reported by cause of death.
Time frame: Baseline through study completion (up to 52 weeks)
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IMC-RON8 | Number of Participants Who Died | Death Due to PD | 3 Participants |
| IMC-RON8 | Number of Participants Who Died | Death, Cause Unknown | 0 Participants |
| IMC-RON8 (10 mg/kg qw) | Number of Participants Who Died | Death Due to PD | 1 Participants |
| IMC-RON8 (10 mg/kg qw) | Number of Participants Who Died | Death, Cause Unknown | 0 Participants |
| IMC-RON8 (15 mg/kg qw) | Number of Participants Who Died | Death Due to PD | 1 Participants |
| IMC-RON8 (15 mg/kg qw) | Number of Participants Who Died | Death, Cause Unknown | 0 Participants |
| IMC-RON8 (20 mg/kg qw) | Number of Participants Who Died | Death Due to PD | 4 Participants |
| IMC-RON8 (20 mg/kg qw) | Number of Participants Who Died | Death, Cause Unknown | 0 Participants |
| IMC-RON8 (15 mg/kg q2w) | Number of Participants Who Died | Death Due to PD | 1 Participants |
| IMC-RON8 (15 mg/kg q2w) | Number of Participants Who Died | Death, Cause Unknown | 0 Participants |
| IMC-RON8 (20 mg/kg q2w) | Number of Participants Who Died | Death Due to PD | 1 Participants |
| IMC-RON8 (20 mg/kg q2w) | Number of Participants Who Died | Death, Cause Unknown | 0 Participants |
| IMC-RON8 (30 mg/kg q2w) | Number of Participants Who Died | Death, Cause Unknown | 0 Participants |
| IMC-RON8 (30 mg/kg q2w) | Number of Participants Who Died | Death Due to PD | 0 Participants |
| IMC-RON8 (40 mg/kg q2w) | Number of Participants Who Died | Death Due to PD | 0 Participants |
| IMC-RON8 (40 mg/kg q2w) | Number of Participants Who Died | Death, Cause Unknown | 1 Participants |