Neoplasms
Conditions
Keywords
Advanced Solid Tumors
Brief summary
A dose escalation study to determine the safety and maximum tolerated dose (MTD) of IMC-3C5 in subjects with advanced solid tumors that are refractory to standard therapy or for which no standard therapy is available.
Detailed description
This multicenter study will enroll approximately 40 participants. The actual sample size will vary depending on how many participants are needed to obtain at least 3 complete participants per cohort. IMC-3C5 will initially be administered once every week (Cohorts 1-4) in a dose escalated manner. The starting dose will be 5 mg/kg weekly (Cohort 1). Dose escalation will proceed to 10 mg/kg (Cohort 2), 20 mg/kg (Cohort 3), and 30 mg/kg (Cohort 4). Based on an analysis of the safety and pharmacokinetic profile of weekly dosing, participants may be enrolled sequentially into 2 every-other-week dose cohorts (Cohorts 5-6, 20 mg/kg and 30 mg/kg). Intermediate doses may also be used.
Interventions
BIOLOGICALIMC-3C5
Escalating doses of IMC-3C5 administered intravenously (i.v.), weekly or every other week
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant has histologic or cytologic confirmation of cancer 2. Participant has an advanced solid tumor that is refractory to standard therapy or for which no standard therapy is available 3. Participant has measurable or nonmeasurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 4. Participant has not received prior chemotherapy or prior treatment with an investigational agent or device within 28 days prior to enrollment(hormone therapy is acceptable) 5. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1, or 2 6. Participant has adequate hematologic, hepatic, renal, and coagulation function 7. Participant has a life expectancy greater than 3 months 8. Participant agrees to use adequate contraception during the study period and for 12 weeks after last dose of investigational agent
Exclusion criteria
1. Participant has a known sensitivity to monoclonal antibodies or other therapeutic proteins, or to agents of similar biologic composition as IMC-3C5 2. Participant has received treatment with any monoclonal antibodies including bevacizumab within 6 weeks prior to enrollment 3. Participant has undergone a major surgical procedure, radiation therapy, open biopsy, or has experienced a significant injury within 28 days prior to enrollment 4. Participant has an ongoing or active infection (except as outlined in Exclusion Criterion #11), congestive heart failure, active bleeding or any other serious uncontrolled medical disorder 5. Participant has known or suspected untreated brain or leptomeningeal metastases 6. Participant has uncontrolled hypertension 7. Participant has received an organ transplant 8. Participant has a serious or nonhealing wound, ulcer, or bone fracture 9. Participant has experienced an arterial or venous thromboembolic event within 6 months prior to enrollment 10. Participant currently has peripheral edema requiring diuresis or anasarca 11. Participant has Human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), except subjects who have been on a stable antiviral regimen for at least 12 weeks, have a viral load of \< 50 copies/mL, and a CD4 count of ≥ 200 cells/mm3 12. Participant is currently using or has received a thrombolytic agent within 28 days prior to enrollment 13. Participant is receiving aspirin at a dose higher than 325 mg per day or full-dose anticoagulation 14. Participant if female, is pregnant or is lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Baseline up to 46 months | AEs include serious AEs (SAEs). AEs do not distinguish whether the events are treatment-emergent. A summary of serious and other non-serious AEs, regardless of causality, is presented in the Reported Adverse Event module. |
| Number of Participants Reporting Dose-Limiting Toxicity (DLT) | Baseline up to 16 Months | A DLT was defined as any adverse event (National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\], Version 4.0) considered by the investigator to be definitely, probably, or possibly related to IMC-3C5, that occurred during the DLT Assessment Period (weeks 1 through 6) as follows: * Any Grade 3 or 4 hematologic toxicity * Any Grade 3 or 4 nonhematologic toxicity (excluding fatigue or anorexia lasting \<7 days, or Grade 3 nausea and/or vomiting that persisted for \<2 days following appropriate supportive care intervention) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Drug Concentration (AUC 0-tlast) of IMC-3C5 - First Infusion | Prior to 1st infusion (Day 1 of Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.) | — |
| Maximum Concentration (Cmax) of IMC-3C5 - Fourth Infusion | Prior to 4th infusion (approximately Day 22, Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. Prior to 4th infusion, 1 hour post infusion for cohort 5. (Cycle 1 = 4-6 weeks.) | — |
| Area Under the Concentration-Time Curve During One Dose Interval (AUCtau) of IMC-3C5 (168 Hours) - Fourth Infusion | Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.) | — |
| Terminal Half-life (t1/2) of IMC-3C5 - Fourth Infusion | Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.) | — |
| Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Baseline up to 46 Months | Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Progressive Disease (PD) was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir. Stable Disease (SD) was defined as small changes that did not meet above criteria. |
| Clearance (Cl) of IMC-3C5 at Steady State - Fourth Infusion | Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.) | — |
| Minimum Concentration (Cmin) of IMC-3C5 - Fourth Infusion | Prior to 4th infusion (approximately Day 22) of Cycle 1 for cohorts 1-5. (Cycle 1 = 4 - 6 weeks.) | Trough concentration (Ctrough) prior to fourth infusion of Cycle 1. |
| Anti-IMC-3C5 Antibody Assessment | Predose: First and fourth infusions (Cycle 1), ninth infusion (Cycle 3), 15th infusion (Cycle 4), 21st infusion (Cycle 6), 27th infusion (Cycle 7). (Cycle 1 = 4 - 6 weeks. Subsequent cycles = 4 weeks.) | — |
| Volume of Distribution of IMC-3C5 at Steady State (Vss) - Fourth Infusion | Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.) | — |
| Maximum Concentration (Cmax) of IMC-3C5 - First Infusion | Prior to 1st infusion (Day 1 of Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168 hours post infusion for cohorts 1-4. Prior to 1st infusion and 1 hour post infusion for cohort 5. (Cycle 1 = 4 - 6 weeks.) | — |
Countries
United States
Participant flow
Pre-assignment details
Cohorts 1-4: Trial completion was defined as completion of the dose-limiting toxicity (DLT) period (4 weeks of IMC-3C5 followed by 2 weeks without drug) or IMC-3C5 discontinuation due to DLT. Cohort 5: Trial completion indicated that participants were fully observed for primary and secondary outcomes.
Participants by arm
| Arm | Count |
|---|---|
| 5 mg/kg IMC-3C5 Cohort 1: 5 milligrams/kilogram (mg/kg) IMC-3C5 administered intravenously (IV) once per week for four weeks (4 week treatment cycle). First treatment cycle is followed by two-week rest period (no drug).
After 1 cycle of treatment, participants with complete or partial response or stable disease were permitted to receive IMC-3C5 at the same dose and schedule until disease progression or other withdrawal criterion was met. | 6 |
| 10 mg/kg IMC-3C5 Cohort 2: 10 mg/kg IMC-3C5 administered IV once per week for four weeks (4 week treatment cycle). First treatment cycle is followed by two-week rest period (no drug).
After 1 cycle of treatment, participants with complete or partial response or stable disease were permitted to receive IMC-3C5 at the same dose and schedule until disease progression or other withdrawal criterion was met. | 3 |
| 20 mg/kg IMC-3C5 Cohort 3: 20 mg/kg IMC-3C5 administered IV once per week for four weeks (4 week treatment cycle). First treatment cycle is followed by two-week rest period (no drug).
After 1 cycle of treatment, participants with complete or partial response or stable disease were permitted to receive IMC-3C5 at the same dose and schedule until disease progression or other withdrawal criterion was met. | 3 |
| 30 mg/kg IMC-3C5 Cohort 4: 30 mg/kg IMC-3C5 administered IV once per week for four weeks (4 week treatment cycle). First treatment cycle is followed by two-week rest period (no drug).
After 1 cycle of treatment, participants with complete or partial response or stable disease were permitted to receive IMC-3C5 at the same dose and schedule until disease progression or other withdrawal criterion was met. | 11 |
| 30 mg/kg IMC-3C5 (CRC) Cohort 5: 30 mg/kg IMC-3C5 administered IV once per week for four weeks (4 week treatment cycle) to participants with advanced or metastatic colorectal cancer (CRC).
After 1 cycle of treatment, participants with complete or partial response or stable disease were permitted to receive IMC-3C5 at the same dose and schedule until disease progression or other withdrawal criterion was met. | 21 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Dose limiting toxicity | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | 5 mg/kg IMC-3C5 | Total | 30 mg/kg IMC-3C5 (CRC) | 30 mg/kg IMC-3C5 | 20 mg/kg IMC-3C5 | 10 mg/kg IMC-3C5 |
|---|---|---|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 14.92 | 58.1 years STANDARD_DEVIATION 11.9 | 57.0 years STANDARD_DEVIATION 12.07 | 55.7 years STANDARD_DEVIATION 10.43 | 67.0 years STANDARD_DEVIATION 10.82 | 59.0 years STANDARD_DEVIATION 13.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 44 Participants | 21 Participants | 11 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 4 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 36 Participants | 15 Participants | 10 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 6 Participants | 44 Participants | 21 Participants | 11 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 18 Participants | 9 Participants | 6 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 26 Participants | 12 Participants | 5 Participants | 3 Participants | 1 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 3 / 3 | 3 / 3 | 11 / 11 | 20 / 21 |
| serious Total, serious adverse events | 2 / 6 | 1 / 3 | 1 / 3 | 5 / 11 | 7 / 21 |
Outcome results
Primary
Number of Participants Reporting Dose-Limiting Toxicity (DLT)
A DLT was defined as any adverse event (National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\], Version 4.0) considered by the investigator to be definitely, probably, or possibly related to IMC-3C5, that occurred during the DLT Assessment Period (weeks 1 through 6) as follows: * Any Grade 3 or 4 hematologic toxicity * Any Grade 3 or 4 nonhematologic toxicity (excluding fatigue or anorexia lasting \<7 days, or Grade 3 nausea and/or vomiting that persisted for \<2 days following appropriate supportive care intervention)
Time frame: Baseline up to 16 Months
Population: All participants who received at least one dose of study drug. DLT was assessed in cohorts 1-4, only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 mg/kg IMC-3C5 | Number of Participants Reporting Dose-Limiting Toxicity (DLT) | 1 Participants |
| 10 mg/kg IMC-3C5 | Number of Participants Reporting Dose-Limiting Toxicity (DLT) | 0 Participants |
| 20 mg/kg IMC-3C5 | Number of Participants Reporting Dose-Limiting Toxicity (DLT) | 0 Participants |
| 30 mg/kg IMC-3C5 | Number of Participants Reporting Dose-Limiting Toxicity (DLT) | 0 Participants |
Primary
Number of Participants With Adverse Events (AEs)
AEs include serious AEs (SAEs). AEs do not distinguish whether the events are treatment-emergent. A summary of serious and other non-serious AEs, regardless of causality, is presented in the Reported Adverse Event module.
Time frame: Baseline up to 46 months
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 mg/kg IMC-3C5 | Number of Participants With Adverse Events (AEs) | 6 Participants |
| 10 mg/kg IMC-3C5 | Number of Participants With Adverse Events (AEs) | 3 Participants |
| 20 mg/kg IMC-3C5 | Number of Participants With Adverse Events (AEs) | 3 Participants |
| 30 mg/kg IMC-3C5 | Number of Participants With Adverse Events (AEs) | 11 Participants |
| 30 mg/kg IMC-3C5 (CRC) | Number of Participants With Adverse Events (AEs) | 20 Participants |
Secondary
Anti-IMC-3C5 Antibody Assessment
Time frame: Predose: First and fourth infusions (Cycle 1), ninth infusion (Cycle 3), 15th infusion (Cycle 4), 21st infusion (Cycle 6), 27th infusion (Cycle 7). (Cycle 1 = 4 - 6 weeks. Subsequent cycles = 4 weeks.)
Population: Zero participants were analyzed. No assay was available to assess serum anti-IMC-3C5 antibodies.
Secondary
Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR)
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Progressive Disease (PD) was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir. Stable Disease (SD) was defined as small changes that did not meet above criteria.
Time frame: Baseline up to 46 Months
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Stable disease | 1 Participants |
| 5 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Not evaluable | 1 Participants |
| 5 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Progressive disease | 4 Participants |
| 10 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Progressive disease | 2 Participants |
| 10 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Stable disease | 1 Participants |
| 10 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Not evaluable | 0 Participants |
| 20 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Progressive disease | 3 Participants |
| 20 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Stable disease | 0 Participants |
| 20 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Not evaluable | 0 Participants |
| 30 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Stable disease | 2 Participants |
| 30 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Not evaluable | 3 Participants |
| 30 mg/kg IMC-3C5 | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Progressive disease | 6 Participants |
| 30 mg/kg IMC-3C5 (CRC) | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Progressive disease | 11 Participants |
| 30 mg/kg IMC-3C5 (CRC) | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Stable disease | 4 Participants |
| 30 mg/kg IMC-3C5 (CRC) | Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) | Not evaluable | 6 Participants |
Secondary
Area Under the Concentration-Time Curve During One Dose Interval (AUCtau) of IMC-3C5 (168 Hours) - Fourth Infusion
Time frame: Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.)
Population: AUCtau was only measured in participants in cohorts 1-4 who received study drug and had sufficient evaluable AUCtau values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg IMC-3C5 | Area Under the Concentration-Time Curve During One Dose Interval (AUCtau) of IMC-3C5 (168 Hours) - Fourth Infusion | 20400 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 24 |
| 10 mg/kg IMC-3C5 | Area Under the Concentration-Time Curve During One Dose Interval (AUCtau) of IMC-3C5 (168 Hours) - Fourth Infusion | 47300 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 28 |
| 20 mg/kg IMC-3C5 | Area Under the Concentration-Time Curve During One Dose Interval (AUCtau) of IMC-3C5 (168 Hours) - Fourth Infusion | 81800 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 22 |
| 30 mg/kg IMC-3C5 | Area Under the Concentration-Time Curve During One Dose Interval (AUCtau) of IMC-3C5 (168 Hours) - Fourth Infusion | 122000 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 18 |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Drug Concentration (AUC 0-tlast) of IMC-3C5 - First Infusion
Time frame: Prior to 1st infusion (Day 1 of Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.)
Population: AUC 0-tlast was only measured in participants in cohorts 1-4, who received study drug and had sufficient evaluable AUC 0-tlast values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg IMC-3C5 | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Drug Concentration (AUC 0-tlast) of IMC-3C5 - First Infusion | 9550 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 28 |
| 10 mg/kg IMC-3C5 | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Drug Concentration (AUC 0-tlast) of IMC-3C5 - First Infusion | 22400 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 24 |
| 20 mg/kg IMC-3C5 | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Drug Concentration (AUC 0-tlast) of IMC-3C5 - First Infusion | 37100 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 12 |
| 30 mg/kg IMC-3C5 | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Drug Concentration (AUC 0-tlast) of IMC-3C5 - First Infusion | 59900 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 30 |
Secondary
Clearance (Cl) of IMC-3C5 at Steady State - Fourth Infusion
Time frame: Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.)
Population: Cl was only measured in participants in cohorts 1-4 who received study drug and had sufficient evaluable Cl values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg IMC-3C5 | Clearance (Cl) of IMC-3C5 at Steady State - Fourth Infusion | 0.0198 Liter/hour (L/h) | Geometric Coefficient of Variation 39 |
| 10 mg/kg IMC-3C5 | Clearance (Cl) of IMC-3C5 at Steady State - Fourth Infusion | 0.0192 Liter/hour (L/h) | Geometric Coefficient of Variation 29 |
| 20 mg/kg IMC-3C5 | Clearance (Cl) of IMC-3C5 at Steady State - Fourth Infusion | 0.0181 Liter/hour (L/h) | Geometric Coefficient of Variation 27 |
| 30 mg/kg IMC-3C5 | Clearance (Cl) of IMC-3C5 at Steady State - Fourth Infusion | 0.0191 Liter/hour (L/h) | Geometric Coefficient of Variation 19 |
Secondary
Maximum Concentration (Cmax) of IMC-3C5 - First Infusion
Time frame: Prior to 1st infusion (Day 1 of Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168 hours post infusion for cohorts 1-4. Prior to 1st infusion and 1 hour post infusion for cohort 5. (Cycle 1 = 4 - 6 weeks.)
Population: All participants who received study drug and had sufficient evaluable Cmax values. For cohort 5, 1-hour post infusion values are presented.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg IMC-3C5 | Maximum Concentration (Cmax) of IMC-3C5 - First Infusion | 110 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 21 |
| 10 mg/kg IMC-3C5 | Maximum Concentration (Cmax) of IMC-3C5 - First Infusion | 259 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 26 |
| 20 mg/kg IMC-3C5 | Maximum Concentration (Cmax) of IMC-3C5 - First Infusion | 435 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 15 |
| 30 mg/kg IMC-3C5 | Maximum Concentration (Cmax) of IMC-3C5 - First Infusion | 689 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 18 |
| 30 mg/kg IMC-3C5 (CRC) | Maximum Concentration (Cmax) of IMC-3C5 - First Infusion | 711 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 27 |
Secondary
Maximum Concentration (Cmax) of IMC-3C5 - Fourth Infusion
Time frame: Prior to 4th infusion (approximately Day 22, Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. Prior to 4th infusion, 1 hour post infusion for cohort 5. (Cycle 1 = 4-6 weeks.)
Population: All participants who received study drug and had sufficient evaluable Cmax values. For cohort 5, 1-hour post infusion values are presented.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg IMC-3C5 | Maximum Concentration (Cmax) of IMC-3C5 - Fourth Infusion | 198 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 13 |
| 10 mg/kg IMC-3C5 | Maximum Concentration (Cmax) of IMC-3C5 - Fourth Infusion | 456 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 22 |
| 20 mg/kg IMC-3C5 | Maximum Concentration (Cmax) of IMC-3C5 - Fourth Infusion | 754 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 17 |
| 30 mg/kg IMC-3C5 | Maximum Concentration (Cmax) of IMC-3C5 - Fourth Infusion | 1150 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 16 |
| 30 mg/kg IMC-3C5 (CRC) | Maximum Concentration (Cmax) of IMC-3C5 - Fourth Infusion | 1130 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 23 |
Secondary
Minimum Concentration (Cmin) of IMC-3C5 - Fourth Infusion
Trough concentration (Ctrough) prior to fourth infusion of Cycle 1.
Time frame: Prior to 4th infusion (approximately Day 22) of Cycle 1 for cohorts 1-5. (Cycle 1 = 4 - 6 weeks.)
Population: All participants who received study drug and had sufficient evaluable Ctrough values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg IMC-3C5 | Minimum Concentration (Cmin) of IMC-3C5 - Fourth Infusion | 72.4 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 37 |
| 10 mg/kg IMC-3C5 | Minimum Concentration (Cmin) of IMC-3C5 - Fourth Infusion | 175 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 37 |
| 20 mg/kg IMC-3C5 | Minimum Concentration (Cmin) of IMC-3C5 - Fourth Infusion | 246 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 20 |
| 30 mg/kg IMC-3C5 | Minimum Concentration (Cmin) of IMC-3C5 - Fourth Infusion | 430 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 25 |
| 30 mg/kg IMC-3C5 (CRC) | Minimum Concentration (Cmin) of IMC-3C5 - Fourth Infusion | 416 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 30 |
Secondary
Terminal Half-life (t1/2) of IMC-3C5 - Fourth Infusion
Time frame: Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.)
Population: t1/2 was estimated in participants in cohorts 1-4 who received study drug and had sufficient evaluable t1/2 values.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 5 mg/kg IMC-3C5 | Terminal Half-life (t1/2) of IMC-3C5 - Fourth Infusion | 11.7 days |
| 10 mg/kg IMC-3C5 | Terminal Half-life (t1/2) of IMC-3C5 - Fourth Infusion | 8.45 days |
| 20 mg/kg IMC-3C5 | Terminal Half-life (t1/2) of IMC-3C5 - Fourth Infusion | 8.97 days |
| 30 mg/kg IMC-3C5 | Terminal Half-life (t1/2) of IMC-3C5 - Fourth Infusion | 10.4 days |
Secondary
Volume of Distribution of IMC-3C5 at Steady State (Vss) - Fourth Infusion
Time frame: Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.)
Population: Cohorts 1 - 3: Data not presented because extrapolated AUC was more than 30% and estimated Vss values may not be reliable. Cohort 4: All participants who received study drug and had sufficient evaluable Vss values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg IMC-3C5 | Volume of Distribution of IMC-3C5 at Steady State (Vss) - Fourth Infusion | 6.67 Liter (L) | Geometric Coefficient of Variation 8 |