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

Soft Tissue Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03126591
• Other study ID #: 15847
• Secondary ID: I5B-MC-JGDQ2016-
• Status: Completed
• Phase: Phase 1
• Start date: July 3, 2017
• Est. completion date: February 21, 2023

Study information

• Verified date: April 2023
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: February 21, 2023
• Est. primary completion date: May 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Sarcoma
• Soft Tissue Sarcoma

Intervention

Drug:
• Olaratumab
Administered IV
• Pembrolizumab
Administered IV

Locations

Country	Name	City	State
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Denmark	Herlev and Gentofte Hospital	Herlev
France	Gustave Roussy	Villejuif Cedex
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cycle 1 (21 Days)
Secondary	Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab	PK: Cmax of olaratumab	Post-dose on Days 1 and 8 of Cycles 1 and 3 (21 Day Cycles)
Secondary	PK: Minimum Serum Concentration (Cmin) of Olaratumab	PK: Cmin of olaratumab	Pre-dose on Day 1 of Cycles 2 and 4 (21 Day Cycles)
Secondary	PK: Elimination Half-Life of Olaratumab	PK: Elimination half-life of olaratumab	Days 8 to 21 of Cycles 1 and 3 (21 Day Cycles)
Secondary	Number of Participants with Anti-Olaratumab Antibodies When Administered in Combination with Pembrolizumab	Number of participants with anti-olaratumab antibodies	Predose Cycle 1 Day 1 through Follow Up (Approximately 30 Months)
Secondary	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	Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 18 Months)
Secondary	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	Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 18 Months)
Secondary	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	Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 30 Months)
Secondary	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	Baseline to Measured Progressive Disease or Death Due to Any Cause (Approximately 18 Months)
Secondary	Overall Survival (OS)	OS defined as the time from the date of randomization to the date of death from any cause	Baseline to Death from Any Cause (Approximately 30 Months)

External Links

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