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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01316263
• Collaborator: (none)
• Enrollment: 21
• Locations: 13
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumor (GIST)	Biological: Olaratumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Tumor Response of Stable Disease (SD), Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate) at 12 Weeks [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.

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [Baseline to the first date of objectively determined PD or death from any cause up to 35.9 weeks]

   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.

2. Percentage of Participants With CR or PR [Radiographic Objective Response Rate (ORR)] [Baseline up to 35.9 weeks and post study discontinuation 30-day follow-up]

   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.

3. Overall Survival (OS) [Date of first dose of study drug to the date of death from any cause up to 57.3 weeks]

   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.

4. Number of Participants With Adverse Events (AE) and Participants Who Died [Baseline up to 57.3 weeks and 30-day post study-discontinuation follow-up]

   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.

5. Percentage of Participants With CR, PR or SD [Disease Control Rate (DCR)] [Baseline up to 35.9 weeks]

   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.

6. Maximum Concentration (Cmax) [Day 1 of Cycles 1 and 3 (14-day cycles)]

7. Area Under the Curve (AUC) [Day 1 of Cycles 1 and 3 (14-day cycles)]

8. Half Life (t½) [Day 1 of Cycles 1 and 3 (14-day cycles)]

9. Clearance (CL) [Day 1 of Cycles 1 and 3 (14-day cycles)]

10. Volume of Distribution at Steady State (Vss) [Day 1 of Cycles 1 and 3 (14-day cycles)]

11. Percentage of Participants With Human Anti-Olaratumab (IMC-3G3) Antibody Results [Day 1 of Cycles 1, 3, 6, 12 and 18 prior to infusion (14-day cycles)]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ImClone Investigational Site	Chicago	Illinois	United States	60637
2	ImClone Investigational Site	Boston	Massachusetts	United States	02215
3	ImClone Investigational Site	Edegem		Belgium	B-2650
4	ImClone Investigational Site	Leuven		Belgium	B-3000
5	ImClone Investigational Site	Bad Saarow		Germany	15526
6	ImClone Investigational Site	Berlin		Germany	13125
7	ImClone Investigational Site	Essen		Germany	45122
8	ImClone Investigational Site	Mannheim		Germany	68167
9	ImClone Investigational Site	Tuebingen		Germany	72076
10	ImClone Investigational Site	Leiden		Netherlands	2300 RC
11	ImClone Investigational Site	Warsaw		Poland	02-781
12	ImClone Investigational Site	Madrid		Spain	28041
13	ImClone Investigational Site	Madrid		Spain	28050

Sponsors and Collaborators

• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01316263
• Other Study ID Numbers: 14244; CP15-1008; I5B-IE-JGDH; 2010-022560-12
• First Posted: Mar 16, 2011
• Last Update Posted: Mar 9, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Gastrointestinal Stromal Tumors; Olaratumab

Study Results

Participant Flow

Pre-assignment Detail	Participants who were considered to have completed Stage 1 of the study discontinued due to progressive disease (PD) or died.

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 milligrams per kilogram (mg/kg) of Olaratumab (IMC-3G3) was administered intravenously (IV) on Day 1 of each cycle (14-day cycles) to participants with gastrointestinal stromal tumors (GIST) with genotypes that had a platelet-derived growth factor receptor alpha (PDGFRα) mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
Period Title: Overall Study
STARTED	7	14
Received Any Study Drug	7	14
COMPLETED	7	14
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)	Total
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.	Total of all reporting groups
Overall Participants	7	14	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.9 (7.90)	48.9 (9.11)	54.2 (11.48)
Sex: Female, Male (Count of Participants)
Female	2 28.6%	7 50%	9 42.9%
Male	5 71.4%	7 50%	12 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	7 100%	14 100%	21 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	7 100%	14 100%	21 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 28.6%	3 21.4%	5 23.8%
Spain	0 0%	1 7.1%	1 4.8%
Poland	2 28.6%	4 28.6%	6 28.6%
Belgium	1 14.3%	2 14.3%	3 14.3%
Netherlands	0 0%	2 14.3%	2 9.5%
Germany	2 28.6%	2 14.3%	4 19%
Eastern Cooperative Oncology Group Performance Status(ECOG PS) (participants) [Number]
ECOG PS =0	2 28.6%	5 35.7%	7 33.3%
ECOG PS =1	4 57.1%	9 64.3%	13 61.9%
ECOG PS ≥2	1 14.3%	0 0%	1 4.8%
Type of Cancer-Gastrointestinal Stromal Tumor (participants) [Number]
Number [participants]	7 100%	14 100%	21 100%
Histology-Cell Type (participants) [Number]
Epitheloid Cell	6 85.7%	0 0%	6 28.6%
Spindle Cell	0 0%	9 64.3%	9 42.9%
Mixed/Combined	0 0%	4 28.6%	4 19%
Other-unspecified	1 14.3%	1 7.1%	2 9.5%
Initial T Classification Staging at Diagnosis (participants) [Number]
Tis	0 0%	1 7.1%	1 4.8%
T2	1 14.3%	3 21.4%	4 19%
T3	0 0%	4 28.6%	4 19%
T4	3 42.9%	1 7.1%	4 19%
TX	1 14.3%	4 28.6%	5 23.8%
Missing	2 28.6%	1 7.1%	3 14.3%
Initial N Classification Staging at Diagnosis (participants) [Number]
N0	5 71.4%	11 78.6%	16 76.2%
N1	0 0%	1 7.1%	1 4.8%
Missing	2 28.6%	2 14.3%	4 19%
Initial M Stage at Diagnosis (participants) [Number]
M0	4 57.1%	7 50%	11 52.4%
M1	1 14.3%	5 35.7%	6 28.6%
MX	0 0%	1 7.1%	1 4.8%
Missing	2 28.6%	1 7.1%	3 14.3%
Current T Classification Staging (participants) [Number]
T0	2 28.6%	2 14.3%	4 19%
T3	0 0%	4 28.6%	4 19%
T4	2 28.6%	2 14.3%	4 19%
TX	2 28.6%	4 28.6%	6 28.6%
Unknown	0 0%	1 7.1%	1 4.8%
Missing	1 14.3%	1 7.1%	2 9.5%
Current N Classification Staging (participants) [Number]
N0	5 71.4%	8 57.1%	13 61.9%
N1	0 0%	3 21.4%	3 14.3%
N2	1 14.3%	0 0%	1 4.8%
Missing	1 14.3%	3 21.4%	4 19%
Current M Classification Staging (participants) [Number]
M1	6 85.7%	13 92.9%	19 90.5%
Missing	1 14.3%	1 7.1%	2 9.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Tumor Response of Stable Disease (SD), Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate) at 12 Weeks
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All participants who received any study drug.

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
Measure Participants	7	14
Number (90% Confidence Interval) [percentage of participants]	42.9 612.9%	14.3 102.1%

2. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	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.
Time Frame	Baseline to the first date of objectively determined PD or death from any cause up to 35.9 weeks

Outcome Measure Data

Analysis Population Description

All participants who received any study drug. Censored participants: PDGFRα Mutant=2, PDGFRα Wild-Type=0.

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
Measure Participants	7	14
Median (90% Confidence Interval) [weeks]	32.1	6.1

3. Secondary Outcome

Title	Percentage of Participants With CR or PR [Radiographic Objective Response Rate (ORR)]
Description	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.
Time Frame	Baseline up to 35.9 weeks and post study discontinuation 30-day follow-up

Outcome Measure Data

Analysis Population Description

All participants who received any study drug.

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
Measure Participants	7	14
Number (90% Confidence Interval) [percentage of participants]	0 0%	0 0%

4. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	Date of first dose of study drug to the date of death from any cause up to 57.3 weeks

Outcome Measure Data

Analysis Population Description

All participants who received any study drug. Participants censored: PDGFRα Mutant=4, PDGFRα Wild-type=4.

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
Measure Participants	7	14
Median (90% Confidence Interval) [weeks]	NA	24.9

5. Secondary Outcome

Title	Number of Participants With Adverse Events (AE) and Participants Who Died
Description	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.
Time Frame	Baseline up to 57.3 weeks and 30-day post study-discontinuation follow-up

Outcome Measure Data

Analysis Population Description

All participants who received any study drug.

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
Measure Participants	7	14
SAEs	2 28.6%	3 21.4%
AEs	7 100%	13 92.9%
Died Due to AE	0 0%	1 7.1%
Died Due to Disease Progression	0 0%	1 7.1%

6. Secondary Outcome

Title	Percentage of Participants With CR, PR or SD [Disease Control Rate (DCR)]
Description	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.
Time Frame	Baseline up to 35.9 weeks

Outcome Measure Data

Analysis Population Description

All participants who received any study drug.

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
Measure Participants	7	14
Number (90% Confidence Interval) [percentage of participants]	71.4 1020%	28.6 204.3%

7. Secondary Outcome

Title	Maximum Concentration (Cmax)
Time Frame	Day 1 of Cycles 1 and 3 (14-day cycles)

Outcome Measure Data

Analysis Population Description

All participants who had evaluable pharmacokinetic (PK) Cmax results at the specific time point. Due to the limited data, Cmax is not representative of the study population.

Arm/Group Title	Olaratumab (IMC-3G3)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation or PDGFRα wild type.
Measure Participants	3
Day 1 Cycle 1 (n=2)	392.9
Day 1 Cycle 3 (n=1)	483.9

8. Secondary Outcome

Title	Area Under the Curve (AUC)
Time Frame	Day 1 of Cycles 1 and 3 (14-day cycles)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. AUC was not reported. AUC could not be calculated due to an insufficient number of olaratumab serum concentrations.

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
Measure Participants	0	0

9. Secondary Outcome

Title	Half Life (t½)
Time Frame	Day 1 of Cycles 1 and 3 (14-day cycles)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. t1/2 was not reported. t1/2 could not be calculated due to an insufficient number of olaratumab serum concentrations.

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
Measure Participants	0	0

10. Secondary Outcome

Title	Clearance (CL)
Time Frame	Day 1 of Cycles 1 and 3 (14-day cycles)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. CL was not reported. CL could not be calculated due to an insufficient number of olaratumab serum concentrations.

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
Measure Participants	0	0

11. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss)
Time Frame	Day 1 of Cycles 1 and 3 (14-day cycles)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. Vss was not reported. Vss could not be calculated due to an insufficient number of olaratumab serum concentrations.

Arm/Group Title	PDGFRα Mutation Positive	PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
Measure Participants	0	0

12. Secondary Outcome

Title	Percentage of Participants With Human Anti-Olaratumab (IMC-3G3) Antibody Results
Description	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.
Time Frame	Day 1 of Cycles 1, 3, 6, 12 and 18 prior to infusion (14-day cycles)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable baseline and evaluable post-baseline antibody data.

Arm/Group Title	PDGFRα Mutation Positive and Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation and that did not have a PDGFRα mutation.
Measure Participants	19
Number [percentage of participants]	5.3 75.7%

Adverse Events

Arm/Group Title	PDGFRα Mutation Positive		PDGFRα Mutation Negative (Wild-Type)
Arm/Group Description	20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that had a PDGFRα mutation.		20 mg/kg of Olaratumab (IMC-3G3) was administered IV on Day 1 of each cycle (14-day cycles) to participants with GIST with genotypes that did not have a PDGFRα mutation.
All Cause Mortality
	PDGFRα Mutation Positive		PDGFRα Mutation Negative (Wild-Type)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PDGFRα Mutation Positive		PDGFRα Mutation Negative (Wild-Type)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)		3/14 (21.4%)
Gastrointestinal disorders
Abdominal pain	1/7 (14.3%)	1	1/14 (7.1%)	1
Ileus	0/7 (0%)	0	1/14 (7.1%)	1
Infections and infestations
Staphylococcal infection	1/7 (14.3%)	1	0/14 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal stromal tumour	0/7 (0%)	0	1/14 (7.1%)	1
Nervous system disorders
Syncope	1/7 (14.3%)	1	0/14 (0%)	0
Other (Not Including Serious) Adverse Events
	PDGFRα Mutation Positive		PDGFRα Mutation Negative (Wild-Type)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		13/14 (92.9%)
Endocrine disorders
Hypothyroidism	1/7 (14.3%)	1	0/14 (0%)	0
Eye disorders
Conjunctival pallor	0/7 (0%)	0	1/14 (7.1%)	1
Gastrointestinal disorders
Abdominal discomfort	2/7 (28.6%)	2	0/14 (0%)	0
Abdominal mass	0/7 (0%)	0	1/14 (7.1%)	1
Abdominal pain	1/7 (14.3%)	1	4/14 (28.6%)	9
Ascites	0/7 (0%)	0	1/14 (7.1%)	1
Constipation	2/7 (28.6%)	2	2/14 (14.3%)	3
Diarrhoea	1/7 (14.3%)	1	1/14 (7.1%)	1
Dysphagia	1/7 (14.3%)	1	0/14 (0%)	0
Nausea	1/7 (14.3%)	1	4/14 (28.6%)	5
Upper gastrointestinal haemorrhage	1/7 (14.3%)	1	0/14 (0%)	0
Vomiting	0/7 (0%)	0	1/14 (7.1%)	2
General disorders
Asthenia	0/7 (0%)	0	1/14 (7.1%)	1
Chest discomfort	1/7 (14.3%)	1	0/14 (0%)	0
Disease progression	0/7 (0%)	0	1/14 (7.1%)	1
Fatigue	4/7 (57.1%)	6	5/14 (35.7%)	7
Influenza like illness	1/7 (14.3%)	1	0/14 (0%)	0
Mucosal inflammation	0/7 (0%)	0	1/14 (7.1%)	1
Non-cardiac chest pain	0/7 (0%)	0	1/14 (7.1%)	1
Oedema peripheral	2/7 (28.6%)	3	2/14 (14.3%)	2
Pyrexia	1/7 (14.3%)	1	1/14 (7.1%)	1
Infections and infestations
Bacterial infection	1/7 (14.3%)	1	0/14 (0%)	0
Nasopharyngitis	0/7 (0%)	0	1/14 (7.1%)	1
Oral herpes	1/7 (14.3%)	1	0/14 (0%)	0
Injury, poisoning and procedural complications
Infusion related reaction	0/7 (0%)	0	3/14 (21.4%)	5
Investigations
Aspartate aminotransferase increased	0/7 (0%)	0	1/14 (7.1%)	1
Blood albumin increased	0/7 (0%)	0	1/14 (7.1%)	1
Blood alkaline phosphatase increased	1/7 (14.3%)	1	1/14 (7.1%)	2
Blood bilirubin increased	0/7 (0%)	0	1/14 (7.1%)	1
Blood calcium increased	1/7 (14.3%)	2	0/14 (0%)	0
Blood lactate dehydrogenase increased	0/7 (0%)	0	1/14 (7.1%)	2
Blood phosphorus decreased	1/7 (14.3%)	1	0/14 (0%)	0
Blood potassium decreased	0/7 (0%)	0	1/14 (7.1%)	1
Blood pressure increased	1/7 (14.3%)	1	0/14 (0%)	0
Breath sounds abnormal	0/7 (0%)	0	1/14 (7.1%)	1
Gamma-glutamyltransferase increased	0/7 (0%)	0	1/14 (7.1%)	1
Haematocrit increased	0/7 (0%)	0	1/14 (7.1%)	1
Haemoglobin increased	0/7 (0%)	0	1/14 (7.1%)	1
Red blood cell count increased	0/7 (0%)	0	1/14 (7.1%)	1
Waist circumference increased	1/7 (14.3%)	1	0/14 (0%)	0
Weight decreased	0/7 (0%)	0	2/14 (14.3%)	3
Metabolism and nutrition disorders
Decreased appetite	2/7 (28.6%)	2	1/14 (7.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/7 (0%)	0	1/14 (7.1%)	2
Back pain	0/7 (0%)	0	1/14 (7.1%)	1
Muscle spasms	0/7 (0%)	0	1/14 (7.1%)	1
Musculoskeletal chest pain	1/7 (14.3%)	1	0/14 (0%)	0
Myalgia	0/7 (0%)	0	1/14 (7.1%)	2
Pain in extremity	1/7 (14.3%)	1	1/14 (7.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bone neoplasm	1/7 (14.3%)	1	0/14 (0%)	0
Nervous system disorders
Headache	0/7 (0%)	0	4/14 (28.6%)	6
Neuralgia	0/7 (0%)	0	1/14 (7.1%)	1
Psychiatric disorders
Tearfulness	0/7 (0%)	0	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/7 (0%)	0	2/14 (14.3%)	4
Dyspnoea	1/7 (14.3%)	1	1/14 (7.1%)	1
Productive cough	0/7 (0%)	0	1/14 (7.1%)	1
Respiratory depression	0/7 (0%)	0	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Dermatitis acneiform	1/7 (14.3%)	1	0/14 (0%)	0
Erythema	0/7 (0%)	0	1/14 (7.1%)	1
Hyperhidrosis	0/7 (0%)	0	1/14 (7.1%)	1
Rash	1/7 (14.3%)	4	0/14 (0%)	0
Vascular disorders
Hypertension	0/7 (0%)	0	1/14 (7.1%)	1

Limitations/Caveats

The development of olaratumab (IMC-3G3) was put on hold in this indication due to reasons not related to efficacy and/or safety, Stage 2 of this study was not completed and trial terminated due to poor accrual.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.