A Study of IMC-CS4 in Subjects With Advanced Solid Tumors

Phase 1 Study of IMC-CS4, a Monoclonal Antibody Targeted to the CSF-1 Receptor (CSF-1R), In Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy is Available

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Biological: IMC-CS4

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic & Research Institute
    • San Francisco, California, United States, 94115
      • Univ of California San Francisco
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • New York
    • New York, New York, United States, 10032
      • Columbia University College of Phys & Surgeons
  • Ohio
    • Cleveland, Ohio, United States, 44106-5055
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMC-CS4 Weight Based Dosing; Participants received 2.5 mg/kg once weekly (QW), 0.3 mg/kg QW, 0.6 mg/kg QW, 1.25 mg/kg every two weeks (Q2W) and1.25 mg/kg QW of IMC CS4 by intravenous infusion in Part A.	Biological: IMC-CS4; Other Names: LY3022855
Experimental: IMC-CS4 Non-Weight Based Dosing; Participants received 100 mg QW, 100 mg QW on weeks 1, 2, 4 and 5 and 150 mg QW of IMC CS4 by intravenous infusion in Part B.	Biological: IMC-CS4; Other Names: LY3022855

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) - Maximum Concentration (Cmax) 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 - Minimum Concentration (Cmin) of IMC-CS4	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 - Area Under the Curve (AUC) 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 - Volume of Distribution at Steady State (Vss) 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 -Clearance (Cl) 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Cycle 1 (6 Days)
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.	Up To 6 Months

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

General Publications

• Dowlati A, Harvey RD, Carvajal RD, Hamid O, Klempner SJ, Kauh JSW, Peterson DA, Yu D, Chapman SC, Szpurka AM, Carlsen M, Quinlan T, Wesolowski R. LY3022855, an anti-colony stimulating factor-1 receptor (CSF-1R) monoclonal antibody, in patients with advanced solid tumors refractory to standard therapy: phase 1 dose-escalation trial. Invest New Drugs. 2021 Aug;39(4):1057-1071. doi: 10.1007/s10637-021-01084-8. Epub 2021 Feb 23.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2011
• Primary Completion (Actual): May 31, 2018
• Study Completion (Actual): May 31, 2018

Study Registration Dates

• First Submitted: April 29, 2011
• First Submitted That Met QC Criteria: April 29, 2011
• First Posted (Estimated): May 3, 2011

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors
• Other Study ID Numbers: 14311; CP24-1001 (Other Identifier: ImClone Systems); I5F-IE-JSCA (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO