A Study of Anti-VEGFR-3 Monoclonal Antibody IMC-3C5 in Subjects With Advanced Solid Tumors

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: Biological: IMC-3C5

• Registration Number: NCT01288989
• Lead Sponsor: Eli Lilly and Company

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.

Study Timeline

• Study First Submitted: 2011-01-31
• Study First Submitted QC: 2011-02-01
• Study First Posted: 2011-02-03
• Study Start: 2011-03
• Primary Completion: 2014-07
• Study Completion: 2014-07
• Status Verified: 2019-03
• Results First Submitted: 2019-03-11
• Results First Submitted QC: 2019-03-11
• Last Update Submitted: 2019-03-11
• Results First Posted: 2019-06-17
• Last Update Posted: 2019-06-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IMC-3C5	IMC-3C5	Participants receiving IMC-3C5 intravenously

Primary Outcome Measures

Name	Time	Method
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)
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.

Secondary Outcome Measures

Name	Time	Method
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.)
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.)
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.
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.)
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.)
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.)
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.)
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.)
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.

Trial Locations

Locations (1)

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, United States