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A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue Sarcoma

Primary Purpose

Soft Tissue Sarcoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Olaratumab
Pembrolizumab
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Soft Tissue Sarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed diagnosis of advanced unresectable or metastatic STS, not amenable to curative treatment and after available standard therapies have failed to provide clinical benefit. Note: Participants with a diagnosis of Grade 1 liposarcoma (atypical lipomatous neoplasms) are eligible if there is histological or radiographic evidence of evolution to more aggressive disease.
  • Presence of measurable or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  • Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
  • Must be able to provide tumor tissue obtained within 6 months of study enrollment. If such tissue is not available, a newly obtained core or excisional biopsy of a tumor lesion must be performed.
  • Have an anticipated life expectancy of ≥3 months.

Exclusion Criteria:

  • Have received any previous systemic therapy (including investigational agents) targeting PD-1/programmed cell death ligand 1 (PDL-1) or PD-1/PDL-2 signaling pathways (including previous participation in Merck MK-3475 trials). Prior treatment with olaratumab is allowed. Prior therapy with other immune checkpoint inhibitors, including but not limited to, anti-CD137 antibody or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, is not permitted.
  • Have known active central nervous system (CNS) metastasis and/or carcinomatous meningitis. Participants with treated CNS metastases are eligible for this study if they have not received corticosteroids and/or anticonvulsants within 7 days of study treatment, and their disease is asymptomatic and radiographically stable for at least 60 days.
  • Have active autoimmune disease or other syndrome that requires systemic steroids or autoimmune agents in the past 2 years.
  • History of interstitial lung disease or non-infectious pneumonia.
  • Have received a live-virus vaccine within 30 days prior to planned treatment start.
  • Have histologically or cytologically confirmed Kaposi's sarcoma or gastrointestinal stromal tumor (GIST).
  • Have inflammatory bowel disease for which the participant has used immunosuppressive agents within the last 2 years.

Sites / Locations

  • Dana Farber Cancer Institute
  • Memorial Sloan Kettering Cancer Center
  • University of Pittsburgh Medical Center
  • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • Herlev and Gentofte Hospital
  • Gustave Roussy

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Olaratumab Dose Level 1 + Pembrolizumab

Olaratumab Dose Level 2 + Pembrolizumab

Olaratumab + Pembrolizumab Expansion

Arm Description

Olaratumab given intravenously (IV) and pembrolizumab given IV.

Olaratumab given IV and pembrolizumab given IV.

Olaratumab given IV and pembrolizumab given IV.

Outcomes

Primary Outcome Measures

Number of Participants with Olaratumab Dose Limiting Toxicities (DLTs)
DLT is defined as an adverse event (AE) during cycle 1 that is possibly related to the study drug and fulfills National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 criteria

Secondary Outcome Measures

Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
PK: Cmax of olaratumab
PK: Minimum Serum Concentration (Cmin) of Olaratumab
PK: Cmin of olaratumab
PK: Elimination Half-Life of Olaratumab
PK: Elimination half-life of olaratumab
Number of Participants with Anti-Olaratumab Antibodies When Administered in Combination with Pembrolizumab
Number of participants with anti-olaratumab antibodies
Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR)
ORR is confirmed best overall tumor response of CR or PR
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease (SD)
DCR defined as CR, PR or SD
Duration of response (DoR)
DoR was defined as the time from the date of the first CR or PR to the first date of progressive disease (PD) or death from any cause
Progression Free Survival (PFS)
PFS is defined as the time from randomization to the first date of objectively determined progressive disease or death from any cause, whichever is earlier
Overall Survival (OS)
OS defined as the time from the date of randomization to the date of death from any cause

Full Information

First Posted
April 17, 2017
Last Updated
April 12, 2023
Sponsor
Eli Lilly and Company
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03126591
Brief Title
A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue Sarcoma
Official Title
An Open-Label, Multicenter, Phase 1a/1b Study of Olaratumab (LY3012207) Plus Pembrolizumab (MK3475) in Patients With Unresectable Locally Advanced or Metastatic Soft Tissue Sarcoma (STS) Who Have Failed Standard Treatments
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
July 3, 2017 (Actual)
Primary Completion Date
May 6, 2021 (Actual)
Study Completion Date
February 21, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety of olaratumab plus pembrolizumab in participants with previously treated advanced or metastatic soft tissue sarcoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Olaratumab Dose Level 1 + Pembrolizumab
Arm Type
Experimental
Arm Description
Olaratumab given intravenously (IV) and pembrolizumab given IV.
Arm Title
Olaratumab Dose Level 2 + Pembrolizumab
Arm Type
Experimental
Arm Description
Olaratumab given IV and pembrolizumab given IV.
Arm Title
Olaratumab + Pembrolizumab Expansion
Arm Type
Experimental
Arm Description
Olaratumab given IV and pembrolizumab given IV.
Intervention Type
Drug
Intervention Name(s)
Olaratumab
Other Intervention Name(s)
LY3012207
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK3475
Intervention Description
Administered IV
Primary Outcome Measure Information:
Title
Number of Participants with Olaratumab Dose Limiting Toxicities (DLTs)
Description
DLT is defined as an adverse event (AE) during cycle 1 that is possibly related to the study drug and fulfills National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 criteria
Time Frame
Cycle 1 (21 Days)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
Description
PK: Cmax of olaratumab
Time Frame
Post-dose on Days 1 and 8 of Cycles 1 and 3 (21 Day Cycles)
Title
PK: Minimum Serum Concentration (Cmin) of Olaratumab
Description
PK: Cmin of olaratumab
Time Frame
Pre-dose on Day 1 of Cycles 2 and 4 (21 Day Cycles)
Title
PK: Elimination Half-Life of Olaratumab
Description
PK: Elimination half-life of olaratumab
Time Frame
Days 8 to 21 of Cycles 1 and 3 (21 Day Cycles)
Title
Number of Participants with Anti-Olaratumab Antibodies When Administered in Combination with Pembrolizumab
Description
Number of participants with anti-olaratumab antibodies
Time Frame
Predose Cycle 1 Day 1 through Follow Up (Approximately 30 Months)
Title
Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR)
Description
ORR is confirmed best overall tumor response of CR or PR
Time Frame
Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 18 Months)
Title
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease (SD)
Description
DCR defined as CR, PR or SD
Time Frame
Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 18 Months)
Title
Duration of response (DoR)
Description
DoR was defined as the time from the date of the first CR or PR to the first date of progressive disease (PD) or death from any cause
Time Frame
Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 30 Months)
Title
Progression Free Survival (PFS)
Description
PFS is defined as the time from randomization to the first date of objectively determined progressive disease or death from any cause, whichever is earlier
Time Frame
Baseline to Measured Progressive Disease or Death Due to Any Cause (Approximately 18 Months)
Title
Overall Survival (OS)
Description
OS defined as the time from the date of randomization to the date of death from any cause
Time Frame
Baseline to Death from Any Cause (Approximately 30 Months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed diagnosis of advanced unresectable or metastatic STS, not amenable to curative treatment and after available standard therapies have failed to provide clinical benefit. Note: Participants with a diagnosis of Grade 1 liposarcoma (atypical lipomatous neoplasms) are eligible if there is histological or radiographic evidence of evolution to more aggressive disease. Presence of measurable or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale. Must be able to provide tumor tissue obtained within 6 months of study enrollment. If such tissue is not available, a newly obtained core or excisional biopsy of a tumor lesion must be performed. Have an anticipated life expectancy of ≥3 months. Exclusion Criteria: Have received any previous systemic therapy (including investigational agents) targeting PD-1/programmed cell death ligand 1 (PDL-1) or PD-1/PDL-2 signaling pathways (including previous participation in Merck MK-3475 trials). Prior treatment with olaratumab is allowed. Prior therapy with other immune checkpoint inhibitors, including but not limited to, anti-CD137 antibody or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, is not permitted. Have known active central nervous system (CNS) metastasis and/or carcinomatous meningitis. Participants with treated CNS metastases are eligible for this study if they have not received corticosteroids and/or anticonvulsants within 7 days of study treatment, and their disease is asymptomatic and radiographically stable for at least 60 days. Have active autoimmune disease or other syndrome that requires systemic steroids or autoimmune agents in the past 2 years. History of interstitial lung disease or non-infectious pneumonia. Have received a live-virus vaccine within 30 days prior to planned treatment start. Have histologically or cytologically confirmed Kaposi's sarcoma or gastrointestinal stromal tumor (GIST). Have inflammatory bowel disease for which the participant has used immunosuppressive agents within the last 2 years.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Herlev and Gentofte Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Gustave Roussy
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France

12. IPD Sharing Statement

Links:
URL
https://trials.lillytrialguide.com/en-US/trial/3VfGy57jAce0UoQ4w2qOwk
Description
A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue Sarcoma

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A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue Sarcoma

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