A Study of Olaratumab (IMC-3G3) in Previously Treated Participants With Unresectable and/or Metastatic Gastrointestinal Stromal Tumors

A Phase 2 Study of a Human Anti-PDGFRα Monoclonal Antibody (IMC-3G3) in Previously Treated Patients With Unresectable and/or Metastatic Gastrointestinal Stromal Tumors (GIST)

The purpose of this study is to evaluate the tumor response of stable disease (SD), partial response (PR), or complete response (CR) [according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1 criteria)] at 12 weeks in participants with Gastrointestinal Stromal Tumors (GIST) harboring platelet-derived growth factor receptor alpha (PDGFRα) mutations and patients with GIST not harboring PDGFRα mutations.

Study Overview

• Status: Terminated
• Conditions: Gastrointestinal Stromal Tumor (GIST)
• Intervention / Treatment: Biological: Olaratumab

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, B-2650
    • ImClone Investigational Site
  • Leuven, Belgium, B-3000
    • ImClone Investigational Site
• Germany
  • Bad Saarow, Germany, 15526
    • ImClone Investigational Site
  • Berlin, Germany, 13125
    • ImClone Investigational Site
  • Essen, Germany, 45122
    • ImClone Investigational Site
  • Mannheim, Germany, 68167
    • ImClone Investigational Site
  • Tuebingen, Germany, 72076
    • ImClone Investigational Site
• Netherlands
  • Leiden, Netherlands, 2300 RC
    • ImClone Investigational Site
• Poland
  • Warsaw, Poland, 02-781
    • ImClone Investigational Site
• Spain
  • Madrid, Spain, 28041
    • ImClone Investigational Site
  • Madrid, Spain, 28050
    • ImClone Investigational Site
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • ImClone Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • ImClone Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant has histologically or cytologically confirmed, unresectable and/or metastatic GIST
• Participant has measurable disease
• Participant has documented objective progression following, or intolerance to, treatment with both imatinib and sunitinib
• Participant's Eastern Cooperative Oncology Group (ECOG) performance status (PS) is 0 to 2

• Participant has either:

  1. prior results from growth factor receptor associated with tyrosine kinase activity (KIT) and PDGFRα mutation analysis that meet analytical criteria as defined for the on-study analysis of these mutations and tumor tissue (from either primary or metastatic tumor) that can be submitted for analysis within 30 days after the first dose of study therapy; or
  2. if prior results from KIT and PDGFRα mutation analysis are not available or do not meet analytical criteria as above, then tumor tissue (from either primary or metastatic tumor) must be submitted for genotype testing at the latest 28 days prior to the first dose of study therapy
• Participant has adequate hematologic, hepatic, renal and coagulation function
• Women of childbearing potential and sexually active males must agree to use adequate contraception prior to study and for at least 12 weeks after the last dose of IMC-3G3
• Participant has a life expectancy of ≥ 3 months

Exclusion Criteria:

• Participant has untreated central nervous system metastases, and as a result, is clinically unstable with regard to neurologic function
• Participant has a history of another primary cancer
• Participant has received any investigational therapy within 14 days prior to registration, or is currently enrolled in any other type of medical research
• Participant is receiving concurrent treatment with other anticancer therapy
• Participant has known human immunodeficiency virus (HIV) infection
• Participant has undergone major surgery within 28 days prior to registration
• If female, participant is pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PDGFRα mutation negative; Participants with GIST with genotypes that do not have a PDGFRα mutation given 20 milligrams per kilogram (mg/kg) Olaratumab intravenously (IV) every 14 days.	Biological: Olaratumab; Administered IV; Other Names: LY3012207; IMC-3G3
Experimental: PDGFRα mutation positive; Participants with GIST with genotypes that have a PDGFRα mutation given 20 mg/kg Olaratumab IV every 14 days.	Biological: Olaratumab; Administered IV; Other Names: LY3012207; IMC-3G3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Tumor Response of Stable Disease (SD), Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate) at 12 Weeks	Clinical benefit was defined as CR, PR, or SD using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST, v1.1) criteria. CR: disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). PR: ≥30% decrease in sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. SD: neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. PD: increase ≥20% in sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). Sum must also have demonstrated an absolute increase of ≥5 mm, or appearance of 1 or more new lesions was considered progression. Percentage of participants=(participants with CR+PR+SD/participants in group) *100.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS defined as the duration from date of first dose of study drug until first radiographic documentation of PD using RECIST, v1.1 criteria or death from any cause. PD defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 mm and the appearance of ≥1 new lesions was progression. Participants who died with no prior PD were considered to have progressed on day of death. Participants who did not progress or were lost to follow-up were censored at date of last radiographic tumor assessment; if no assessment was available censoring was at date of registration. If death or PD occurred after 2 consecutive missing radiographic visits censoring was date of last radiographic visit prior to missed visits. Use of new anticancer therapy prior to PD, censoring was date of last radiographic assessment prior to new therapy.	Baseline to the first date of objectively determined PD or death from any cause up to 35.9 weeks
Percentage of Participants With CR or PR [Radiographic Objective Response Rate (ORR)]	The ORR was the best overall response of CR and PR using RECIST, v1.1 criteria. Participants who did not have a tumor response assessment for any reason were considered nonresponders and were included in the denominator that calculated the response rate. Percentage of participants = (number of participants achieving a response/total of participants treated) * 100.	Baseline up to 35.9 weeks and post study discontinuation 30-day follow-up
Overall Survival (OS)	OS was defined as the time from the date of first dose of study drug to the date of death from any cause. Participants who were alive at the end of the post-study follow-up or were lost to follow-up were censored on the last date the participant was known to be alive.	Date of first dose of study drug to the date of death from any cause up to 57.3 weeks
Number of Participants With Adverse Events (AE) and Participants Who Died	Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs, regardless of causality. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. The number of participants who died due to an AE or disease progression are also reported.	Baseline up to 57.3 weeks and 30-day post study-discontinuation follow-up
Percentage of Participants With CR, PR or SD [Disease Control Rate (DCR)]	DCR defined as CR, PR or SD using RECIST v1.1 criteria. CR was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 mm. PR was defined as ≥30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify PD, taking as reference the smallest sum diameter since the treatment started. PD defined as ≥20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Sum must also have demonstrated an absolute increase of ≥5 mm, or the appearance of 1 or more new lesions was considered progression. Percentage of participants=(number of participants with CR+PR+SD/number of participants in group) * 100.	Baseline up to 35.9 weeks
Maximum Concentration (Cmax)		Day 1 of Cycles 1 and 3 (14-day cycles)
Area Under the Curve (AUC)		Day 1 of Cycles 1 and 3 (14-day cycles)
Half Life (t½)		Day 1 of Cycles 1 and 3 (14-day cycles)
Clearance (CL)		Day 1 of Cycles 1 and 3 (14-day cycles)
Volume of Distribution at Steady State (Vss)		Day 1 of Cycles 1 and 3 (14-day cycles)
Percentage of Participants With Human Anti-Olaratumab (IMC-3G3) Antibody Results	Participants with Treatment Emergent (TE) anti-olaratumab (IMC-3G3) antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.	Day 1 of Cycles 1, 3, 6, 12 and 18 prior to infusion (14-day cycles)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Wagner AJ, Kindler H, Gelderblom H, Schoffski P, Bauer S, Hohenberger P, Kopp HG, Lopez-Martin JA, Peeters M, Reichardt P, Qin A, Nippgen J, Ilaria RL, Rutkowski P. A phase II study of a human anti-PDGFRalpha monoclonal antibody (olaratumab, IMC-3G3) in previously treated patients with metastatic gastrointestinal stromal tumors. Ann Oncol. 2017 Mar 1;28(3):541-546. doi: 10.1093/annonc/mdw659.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: March 14, 2011
• First Submitted That Met QC Criteria: March 15, 2011
• First Posted (Estimate): March 16, 2011

Study Record Updates

• Last Update Posted (Actual): March 9, 2017
• Last Update Submitted That Met QC Criteria: January 27, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Antineoplastic Agents; Olaratumab
• Other Study ID Numbers: 14244; CP15-1008 (Other Identifier: ImClone, LLC); I5B-IE-JGDH (Other Identifier: Eli Lilly and Company); 2010-022560-12 (EudraCT Number)