Neoplasms
Conditions
Keywords
Advanced Solid Tumors
Brief summary
A dose escalation study to establish the safety profile and characterize the pharmacokinetic profile of IMC-CS4 in the treatment of subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy is available.
Interventions
BIOLOGICALIMC-CS4
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has histologic or cytologic confirmation of advanced solid tumors that is refractory to standard therapy or for which no standard therapy is available * Subject has measurable or nonmeasurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 * Subject has resolution to grade ≤1 by NCI-CTCAE (Common Toxicity Criteria for Adverse Effects) Version 4.03 of all clinically significant toxic effects of prior treatment * Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Subject has adequate hematologic, hepatic, renal, and coagulation function * Subject has a life expectancy greater than 3 months * Subject agrees to use adequate contraception during the study period and for 12 weeks after last dose of study therapy * Subject must undergo mandatory biopsies, including one pretreatment and one post treatment tumor biopsy procedure
Exclusion criteria
* Subject has experienced acute pathologic fracture or spinal cord compression within 28 days prior to first dose of study therapy * Subject has a known hypersensitivity to monoclonal antibodies or to agents of similar biologic composition as IMC-CS4. * Subject has received treatment with any monoclonal antibodies within 4 weeks prior to first dose of study therapy * Subject has undergone a major surgical procedure, open biopsy, radiofrequency ablation or has experienced a significant injury within 28 days prior to enrollment * Subject has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer or in situ neoplasm * Subject has an ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, active bleeding or any other serious uncontrolled medical disorder * Subject has known or suspected primary brain or leptomeningeal metastases * Subject has leukemia or lymphoma * Subject is know to have active tuberculosis, leishmaniasis, or listeriosis * Subjects with known history, or clinical or laboratory evidence of liver disease * Subject has a known active hepatitis B or C infection, Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) * Subject if female, is pregnant or breastfeeding * Subject has received an organ transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4 | Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1 | Pharmacokinetics - Minimum concentration (Cmin) of IMC-CS4. |
| Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1 | Pharmacokinetics - Volume of distribution at steady state (Vss) of IMC-CS4. |
| Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1 | Pharmacokinetics -Clearance (Cl) of IMC-CS4. |
| Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1 | Pharmacokinetics (PK) - Maximum concentration (Cmax) of IMC-CS4. |
| Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1 | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Anti-IMC-CS4 Antibody Assessment | Up To 6 Months | The overall percentage of participants with treatment-emergent positive for anti-IMC-CS4 antibodies during the study. Participants were considered positive for anti-IMC-CS4 antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the normal anti-IMC-CS4 level seen in healthy untreated individuals. |
| Recommend Phase 2 Dose (RP2D) of IMC-CS4 | Cycle 1 (6 Days) | The recommended Phase 2 dose was the highest dose where less than 1/3 of participants experienced dose limiting toxicities (DLTs). A DLT is defined as an adverse event (AE) occurring during Cycle 1 that fulfilled 1 of the following criteria: Any Common Terminology Criteria for Adverse Events (CTCAE), version (v) 4.0 Grade 4 neutropenia lasting ≥ 7 days, Grade 3 or 4 neutropenia complicated by fever ≥38.0°C or infection, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia complicated by hemorrhage, Grade 3 or 4 anemia, Grade ≥3 AST/ALT elevation, Grade ≥2 AST/ALT elevation and Grade ≥2 bilirubin elevation and Grade 3 or 4 nonhematologic toxicity. A summary of other nonserious AEs and all Serious Adverse Events (SAE), regardless of causality is located in the Reported Adverse Event section. |
Countries
United States
Participant flow
Pre-assignment details
Completers included participants who died from any cause or disease progression and participants who were alive and on study (either on study treatment or in long term follow-up) at study conclusion.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (2.5 Milligram Per Kilogram (mg/kg) QW) Participants received 2.5 milligram per kilogram (mg/kg) of IMC-CS4 once weekly by intravenous infusion. | 6 |
| Cohort 2 (0.3 mg/kg QW) Participants received 0.3 mg/kg of IMC-CS4 once weekly by intravenous infusion. | 4 |
| Cohort 3 (0.6 mg/kg QW) Participants received 0.6 mg/kg of IMC-CS4 once weekly by intravenous infusion. | 3 |
| Cohort 4 (1.25 mg/kg Q2W) Participants received 1.25 mg/kg of IMC-CS4 every two weeks by intravenous infusion. | 6 |
| Cohort 4 Expanded (1.25 mg/kg Q2W) Participants received 1.25 mg/kg of IMC-CS4 every two weeks by intravenous infusion on weeks 1, 2, 4 and 5. | 5 |
| Cohort 5 (1.25 mg/kg QW) Participants received 1.25 mg/kg of IMC-CS4 weekly once by intravenous infusion. | 5 |
| Cohort 6a (100 mg QW) Participants received 100 mg of IMC-CS4 weekly once by intravenous infusion. | 3 |
| Cohort 6a Expanded (100 mg QW) Participants received 100 mg of IMC-CS4 weekly once by intravenous infusion on weeks 1, 2, 4 and 5. | 11 |
| Cohort 7a (150 mg QW) Participants received 150 mg of IMC-CS4 weekly once by intravenous infusion. | 9 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Non-Compliance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 1 | 0 | 2 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Cohort 1 (2.5 Milligram Per Kilogram (mg/kg) QW) | Total | Cohort 7a (150 mg QW) | Cohort 6a Expanded (100 mg QW) | Cohort 6a (100 mg QW) | Cohort 5 (1.25 mg/kg QW) | Cohort 4 Expanded (1.25 mg/kg Q2W) | Cohort 4 (1.25 mg/kg Q2W) | Cohort 3 (0.6 mg/kg QW) | Cohort 2 (0.3 mg/kg QW) |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.3 Years STANDARD_DEVIATION 6.22 | 58.6 Years STANDARD_DEVIATION 10.43 | 59.1 Years STANDARD_DEVIATION 8.58 | 55.5 Years STANDARD_DEVIATION 12.26 | 54.0 Years STANDARD_DEVIATION 10.15 | 51.6 Years STANDARD_DEVIATION 12.62 | 60.8 Years STANDARD_DEVIATION 13.99 | 63.5 Years STANDARD_DEVIATION 12.57 | 65.0 Years STANDARD_DEVIATION 4.58 | 63.3 Years STANDARD_DEVIATION 1.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 49 Participants | 9 Participants | 9 Participants | 3 Participants | 5 Participants | 5 Participants | 5 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 7 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 38 Participants | 4 Participants | 7 Participants | 3 Participants | 4 Participants | 5 Participants | 5 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 6 Participants | 52 Participants | 9 Participants | 11 Participants | 3 Participants | 5 Participants | 5 Participants | 6 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Female | 3 Participants | 25 Participants | 3 Participants | 7 Participants | 2 Participants | 2 Participants | 4 Participants | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 27 Participants | 6 Participants | 4 Participants | 1 Participants | 3 Participants | 1 Participants | 5 Participants | 1 Participants | 3 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 | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 2 / 4 | 1 / 3 | 1 / 6 | 1 / 5 | 1 / 5 | 1 / 3 | 2 / 11 | 0 / 9 |
| other Total, other adverse events | 6 / 6 | 4 / 4 | 3 / 3 | 6 / 6 | 4 / 5 | 3 / 5 | 3 / 3 | 11 / 11 | 9 / 9 |
| serious Total, serious adverse events | 0 / 6 | 1 / 4 | 2 / 3 | 2 / 6 | 2 / 5 | 3 / 5 | 1 / 3 | 4 / 11 | 3 / 9 |
Outcome results
Primary
Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4
Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4.
Time frame: Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1
Population: All enrolled participants who received at least one dose of study drug and have evaluable PK data for AUC.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 2.5 mg/kg of IMC-CS4 QW | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Cycle 1 Day 1 | 5020 Hours* microgram per mL (h*µg/mL) | Geometric Coefficient of Variation 18 |
| 2.5 mg/kg of IMC-CS4 QW | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Cycle 1 Day 22 | 11300 Hours* microgram per mL (h*µg/mL) | Geometric Coefficient of Variation 18 |
| 0.3 mg/kg of IMC-CS4 QW | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Cycle 1 Day 1 | 256 Hours* microgram per mL (h*µg/mL) | Geometric Coefficient of Variation 14 |
| 0.6 mg/kg of IMC-CS4 QW | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Cycle 1 Day 1 | 492 Hours* microgram per mL (h*µg/mL) | Geometric Coefficient of Variation 23 |
| 1.25 mg/kg of IMC-CS4 QW | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Cycle 1 Day 1 | 1810 Hours* microgram per mL (h*µg/mL) | Geometric Coefficient of Variation 21 |
| 1.25 mg/kg of IMC-CS4 Q2W | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Cycle 1 Day 1 | 1550 Hours* microgram per mL (h*µg/mL) | Geometric Coefficient of Variation 50 |
| 1.25 mg/kg of IMC-CS4 Q2W | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Cycle 1 Day 15 | 1700 Hours* microgram per mL (h*µg/mL) | Geometric Coefficient of Variation 49 |
| 100 mg of IMC-CS4 QW | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Cycle 1 Day 1 | 1780 Hours* microgram per mL (h*µg/mL) | Geometric Coefficient of Variation 43 |
| 100 mg of IMC-CS4 QW | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Cycle 3 Day 1 | 4430 Hours* microgram per mL (h*µg/mL) | Geometric Coefficient of Variation 80 |
| 150 mg of IMC-CS4 QW | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Cycle 3 Day 1 | NA Hours* microgram per mL (h*µg/mL) | — |
| 150 mg of IMC-CS4 QW | Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4 | Cycle 1 Day 1 | 2810 Hours* microgram per mL (h*µg/mL) | Geometric Coefficient of Variation 34 |
Primary
Pharmacokinetics -Clearance (Cl) of IMC-CS4
Pharmacokinetics -Clearance (Cl) of IMC-CS4.
Time frame: Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1
Population: All enrolled participants who received at least one dose of study drug and have evaluable PK data for Clearance.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 2.5 mg/kg of IMC-CS4 QW | Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Cycle 1 Day 1 | 0.0379 Liter per hour (L/h) | Geometric Coefficient of Variation 25 |
| 2.5 mg/kg of IMC-CS4 QW | Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Cycle 1 Day 22 | 0.0195 Liter per hour (L/h) | Geometric Coefficient of Variation 40 |
| 0.3 mg/kg of IMC-CS4 QW | Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Cycle 1 Day 1 | 0.108 Liter per hour (L/h) | Geometric Coefficient of Variation 19 |
| 0.6 mg/kg of IMC-CS4 QW | Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Cycle 1 Day 1 | 0.0715 Liter per hour (L/h) | Geometric Coefficient of Variation 28 |
| 1.25 mg/kg of IMC-CS4 QW | Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Cycle 1 Day 1 | 0.0561 Liter per hour (L/h) | Geometric Coefficient of Variation 30 |
| 1.25 mg/kg of IMC-CS4 Q2W | Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Cycle 1 Day 1 | 0.0566 Liter per hour (L/h) | Geometric Coefficient of Variation 35 |
| 1.25 mg/kg of IMC-CS4 Q2W | Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Cycle 1 Day 15 | 0.0530 Liter per hour (L/h) | Geometric Coefficient of Variation 34 |
| 100 mg of IMC-CS4 QW | Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Cycle 1 Day 1 | 0.0561 Liter per hour (L/h) | Geometric Coefficient of Variation 43 |
| 100 mg of IMC-CS4 QW | Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Cycle 3 Day 1 | 0.0210 Liter per hour (L/h) | Geometric Coefficient of Variation 67 |
| 150 mg of IMC-CS4 QW | Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Cycle 3 Day 1 | NA Liter per hour (L/h) | — |
| 150 mg of IMC-CS4 QW | Pharmacokinetics -Clearance (Cl) of IMC-CS4 | Cycle 1 Day 1 | 0.0534 Liter per hour (L/h) | Geometric Coefficient of Variation 34 |
Primary
Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4
Pharmacokinetics - Minimum concentration (Cmin) of IMC-CS4.
Time frame: Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1
Population: All enrolled participants who received at least one dose of study drug and have evaluable PK data for Cmin.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 2.5 mg/kg of IMC-CS4 QW | Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4 | Cycle 1 Day 22 | 29.9 µg/mL | Geometric Coefficient of Variation 36 |
| 2.5 mg/kg of IMC-CS4 QW | Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4 | Cycle 1 Day 1 | 14.4 µg/mL | Geometric Coefficient of Variation 34 |
| 1.25 mg/kg of IMC-CS4 QW | Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4 | Cycle 1 Day 1 | NA µg/mL | — |
| 1.25 mg/kg of IMC-CS4 Q2W | Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4 | Cycle 1 Day 15 | 3.35 µg/mL | Geometric Coefficient of Variation 22 |
| 1.25 mg/kg of IMC-CS4 Q2W | Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4 | Cycle 1 Day 1 | 3.32 µg/mL | Geometric Coefficient of Variation 11 |
| 100 mg of IMC-CS4 QW | Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4 | Cycle 1 Day 1 | 3.77 µg/mL | Geometric Coefficient of Variation 79 |
| 100 mg of IMC-CS4 QW | Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4 | Cycle 3 Day 1 | 21.9 µg/mL | Geometric Coefficient of Variation 86 |
| 150 mg of IMC-CS4 QW | Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4 | Cycle 3 Day 1 | NA µg/mL | — |
| 150 mg of IMC-CS4 QW | Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4 | Cycle 1 Day 1 | 5.15 µg/mL | Geometric Coefficient of Variation 81 |
Primary
Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4
Pharmacokinetics (PK) - Maximum concentration (Cmax) of IMC-CS4.
Time frame: Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1
Population: All enrolled participants who received at least one dose of study drug and have evaluable PK data for Cmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 2.5 mg/kg of IMC-CS4 QW | Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Cycle 1 Day 22 | 92.7 Microgram/milliliters (µg/mL) | Geometric Coefficient of Variation 23 |
| 2.5 mg/kg of IMC-CS4 QW | Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Cycle 1 Day 1 | 69.2 Microgram/milliliters (µg/mL) | Geometric Coefficient of Variation 13 |
| 0.3 mg/kg of IMC-CS4 QW | Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Cycle 1 Day 1 | 6.83 Microgram/milliliters (µg/mL) | Geometric Coefficient of Variation 32 |
| 0.6 mg/kg of IMC-CS4 QW | Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Cycle 1 Day 1 | 13.5 Microgram/milliliters (µg/mL) | Geometric Coefficient of Variation 33 |
| 1.25 mg/kg of IMC-CS4 QW | Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Cycle 1 Day 1 | 26.0 Microgram/milliliters (µg/mL) | Geometric Coefficient of Variation 14 |
| 1.25 mg/kg of IMC-CS4 Q2W | Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Cycle 1 Day 1 | 31.2 Microgram/milliliters (µg/mL) | Geometric Coefficient of Variation 24 |
| 1.25 mg/kg of IMC-CS4 Q2W | Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Cycle 1 Day 15 | 30.0 Microgram/milliliters (µg/mL) | Geometric Coefficient of Variation 25 |
| 100 mg of IMC-CS4 QW | Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Cycle 1 Day 1 | 32.2 Microgram/milliliters (µg/mL) | Geometric Coefficient of Variation 25 |
| 100 mg of IMC-CS4 QW | Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Cycle 3 Day 1 | 42.8 Microgram/milliliters (µg/mL) | Geometric Coefficient of Variation 59 |
| 150 mg of IMC-CS4 QW | Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Cycle 3 Day 1 | NA Microgram/milliliters (µg/mL) | — |
| 150 mg of IMC-CS4 QW | Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4 | Cycle 1 Day 1 | 42.9 Microgram/milliliters (µg/mL) | Geometric Coefficient of Variation 20 |
Primary
Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4
Pharmacokinetics - Volume of distribution at steady state (Vss) of IMC-CS4.
Time frame: Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1
Population: All enrolled participants who received at least one dose of study drug and have evaluable PK data for Vss.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 2.5 mg/kg of IMC-CS4 QW | Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Cycle 1 Day 1 | 4.80 Liters (L) | Geometric Coefficient of Variation 40 |
| 2.5 mg/kg of IMC-CS4 QW | Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Cycle 1 Day 22 | 6.11 Liters (L) | Geometric Coefficient of Variation 10 |
| 0.3 mg/kg of IMC-CS4 QW | Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Cycle 1 Day 1 | 4.61 Liters (L) | Geometric Coefficient of Variation 4 |
| 0.6 mg/kg of IMC-CS4 QW | Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Cycle 1 Day 1 | 3.21 Liters (L) | Geometric Coefficient of Variation 12 |
| 1.25 mg/kg of IMC-CS4 QW | Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Cycle 1 Day 1 | 4.85 Liters (L) | Geometric Coefficient of Variation 8 |
| 1.25 mg/kg of IMC-CS4 Q2W | Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Cycle 1 Day 1 | 3.59 Liters (L) | Geometric Coefficient of Variation 24 |
| 1.25 mg/kg of IMC-CS4 Q2W | Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Cycle 1 Day 15 | 3.47 Liters (L) | Geometric Coefficient of Variation 19 |
| 100 mg of IMC-CS4 QW | Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Cycle 1 Day 1 | 4.12 Liters (L) | Geometric Coefficient of Variation 14 |
| 100 mg of IMC-CS4 QW | Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Cycle 3 Day 1 | 4.84 Liters (L) | Geometric Coefficient of Variation 60 |
| 150 mg of IMC-CS4 QW | Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Cycle 3 Day 1 | NA Liters (L) | — |
| 150 mg of IMC-CS4 QW | Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4 | Cycle 1 Day 1 | 4.87 Liters (L) | Geometric Coefficient of Variation 26 |
Secondary
Percentage of Participants With Anti-IMC-CS4 Antibody Assessment
The overall percentage of participants with treatment-emergent positive for anti-IMC-CS4 antibodies during the study. Participants were considered positive for anti-IMC-CS4 antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the normal anti-IMC-CS4 level seen in healthy untreated individuals.
Time frame: Up To 6 Months
Population: All enrolled participants who received at least 1 dose of study drug and have baseline and post baseline data for anti-IMC-CS4 antibodies.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2.5 mg/kg of IMC-CS4 QW | Percentage of Participants With Anti-IMC-CS4 Antibody Assessment | 50 Percentage of Participants |
| 0.3 mg/kg of IMC-CS4 QW | Percentage of Participants With Anti-IMC-CS4 Antibody Assessment | 0 Percentage of Participants |
| 0.6 mg/kg of IMC-CS4 QW | Percentage of Participants With Anti-IMC-CS4 Antibody Assessment | 0 Percentage of Participants |
| 1.25 mg/kg of IMC-CS4 QW | Percentage of Participants With Anti-IMC-CS4 Antibody Assessment | 0 Percentage of Participants |
| 1.25 mg/kg of IMC-CS4 Q2W | Percentage of Participants With Anti-IMC-CS4 Antibody Assessment | 0 Percentage of Participants |
| 100 mg of IMC-CS4 QW | Percentage of Participants With Anti-IMC-CS4 Antibody Assessment | 25 Percentage of Participants |
| 150 mg of IMC-CS4 QW | Percentage of Participants With Anti-IMC-CS4 Antibody Assessment | 0 Percentage of Participants |
| Cohort 6a Expanded (100 mg QW) | Percentage of Participants With Anti-IMC-CS4 Antibody Assessment | 18.2 Percentage of Participants |
| Cohort 7a (150 mg QW) | Percentage of Participants With Anti-IMC-CS4 Antibody Assessment | 0 Percentage of Participants |
Secondary
Recommend Phase 2 Dose (RP2D) of IMC-CS4
The recommended Phase 2 dose was the highest dose where less than 1/3 of participants experienced dose limiting toxicities (DLTs). A DLT is defined as an adverse event (AE) occurring during Cycle 1 that fulfilled 1 of the following criteria: Any Common Terminology Criteria for Adverse Events (CTCAE), version (v) 4.0 Grade 4 neutropenia lasting ≥ 7 days, Grade 3 or 4 neutropenia complicated by fever ≥38.0°C or infection, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia complicated by hemorrhage, Grade 3 or 4 anemia, Grade ≥3 AST/ALT elevation, Grade ≥2 AST/ALT elevation and Grade ≥2 bilirubin elevation and Grade 3 or 4 nonhematologic toxicity. A summary of other nonserious AEs and all Serious Adverse Events (SAE), regardless of causality is located in the Reported Adverse Event section.
Time frame: Cycle 1 (6 Days)
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2.5 mg/kg of IMC-CS4 QW | Recommend Phase 2 Dose (RP2D) of IMC-CS4 | 100 milligrams/week |