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

Phase 1

Completed

Conditions: Soft Tissue Sarcoma

Interventions: Drug: Olaratumab
Drug: Pembrolizumab (KEYTRUDA®)

Registration Number: NCT03126591

Lead Sponsor: Eli Lilly and Company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 41

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Expansion	Olaratumab	Participants received 20 mg/kg Olaratumab administered IV on Day 1 and Day 8 in addition to 200 mg Pembrolizumab administered IV on Day 1 of a 21-day cycle.
20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Expansion	Pembrolizumab (KEYTRUDA®)	Participants received 20 mg/kg Olaratumab administered IV on Day 1 and Day 8 in addition to 200 mg Pembrolizumab administered IV on Day 1 of a 21-day cycle.
15 milligrams per kilogram (mg/kg) Olaratumab + 200 milligrams (mg) Pembrolizumab - Dose Escalation	Olaratumab	Participants received15 mg/kg Olaratumab administered IV on Day 1 and Day 8 in addition to 200 mg Pembrolizumab administered IV on Day 1 of a 21-day cycle.
15 milligrams per kilogram (mg/kg) Olaratumab + 200 milligrams (mg) Pembrolizumab - Dose Escalation	Pembrolizumab (KEYTRUDA®)	Participants received15 mg/kg Olaratumab administered IV on Day 1 and Day 8 in addition to 200 mg Pembrolizumab administered IV on Day 1 of a 21-day cycle.
20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Escalation	Olaratumab	Participants received 20 mg/kg Olaratumab administered IV on Day 1 and Day 8 in addition to 200 mg Pembrolizumab administered IV on Day 1 of a 21-day cycle.
20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Escalation	Pembrolizumab (KEYTRUDA®)	Participants received 20 mg/kg Olaratumab administered IV on Day 1 and Day 8 in addition to 200 mg Pembrolizumab administered IV on Day 1 of a 21-day cycle.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)	Cycle 1 (21 Days)	A DLT was defined as an adverse event (AE) during Cycle 1 that is possibly related to the study drug and fulfills any 1 of the following criteria using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0: * Grade ≥3 nonhematologic toxicity, with exceptions * Grade 4 anemia * Grade 4 neutropenia or leukopenia of \>5 days duration * Febrile neutropenia * Grade 3 thrombocytopenia with clinically significant bleeding or Grade 4 thrombocytopenia * Any other significant toxicity deemed to be dose limiting

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab	Cycle 1 and Cycle 3 Day (D) 1: Predose, 1, 2, 5, 24, 96, 168 hours Postdose; Cycle 1 and Cycle 3 Day 8: Predose, 1, 2, 5, 48, 168, 336 hours Postdose	Maximum observed serum concentration of Olaratumab
PK: Minimum Serum Concentration (Cmin) of Olaratumab	Cycle 1 and Cycle 3 Day 1: Predose, 1, 2, 5, 24, 96, 168 hours Postdose; Cycle 1 and Cycle 3 Day 8: Predose, 1, 2, 5, 48, 168, 336 hours Postdose	Cmin was the concentration of olaratumab in the sample taken just prior to the following dose.
PK: Elimination Half-Life (t½) of Olaratumab	Cycle 1 and Cycle 3 Day 1: Predose, 1, 2, 5, 24, 96, 168 hours Postdose; Cycle 1 and Cycle 3 Day 8: Predose, 1, 2, 5, 48, 168, 336 hours Postdose	Terminal elimination half-life of Olaratumab
Number of Participants With Anti-Olaratumab Antibodies (ADA) When Administered in Combination With Pembrolizumab	Predose Cycle 1 Day 1 through Follow Up (up to 6 months)	Detection of ADA in the presence of Olaratumab
Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)	Baseline to Measured Progressive Disease (PD) or Start of New Anti-Cancer Therapy (up to 28 months)	ORR was defined as the percentage of participants who achieved a CR or PR out of all participants treated, measured and recorded by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). CR was defined as the disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm; tumor marker results must have normalized. PR was defined as at least a 30% decrease in the sum diameter of target lesions (taking as reference the baseline sum diameters). Long term follow up began the day after the safety follow up period was completed.
Disease Control Rate (DCR): Percentage of Participants With a Best Response of CR, PR or Stable Disease (SD)	Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (up to 28 months)	DCR was defined according to RECIST v1.1 as the percentage of participants who have achieved CR, PR or stable disease (SD). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Long term follow up began the day after the safety follow up period was completed.
Duration of Response (DoR)	Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (up to 24 months)	DoR was defined according to RECIST v1.1 as the time from the date of the first CR or PR to the first date of PD or death from any cause, whichever is earlier. For each participant who was not known to have died or to have had a progression of disease as of the data inclusion cut-off date, DOR was censored at the date of last objective response assessment prior to the date of any subsequent systemic anticancer therapy. Long term follow up began the day after the safety follow up period was completed.
Progression Free Survival (PFS)	Baseline to Measured Progressive Disease or Death Due to Any Cause (up to 28 months)	Progression-free survival (PFS) time was defined as the time from the date of start of study treatment to the first date of PD (symptomatic or objective) or death due to any cause, whichever occurs first. For participants who were not known to have died or progressed as of the data-inclusion cut-off date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy. Long term follow up began the day after the safety follow up period was completed.
Overall Survival (OS)	Baseline to Death from Any Cause (up to 35 months)	OS was defined as the time from the date of randomization to the date of death from any cause. Data was censored for any participant who was not known to have died or was lost to follow up. Long term follow up began the day after the safety follow up period was completed.

Trial Locations

Locations (6): Gustave Roussy
🇫🇷
Villejuif Cedex, France
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪
Leuven, Belgium
Herlev and Gentofte Hospital
🇩🇰
Herlev, Denmark
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States