Clinical trial NCT03126591: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Soft Tissue Sarcoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-04-24
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (21 Days)
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
timeFrame: 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
measure: PK: Minimum Serum Concentration (Cmin) of Olaratumab
timeFrame: 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
measure: PK: Elimination Half-Life (t½) of Olaratumab
timeFrame: 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
measure: Number of Participants With Anti-Olaratumab Antibodies (ADA) When Administered in Combination With Pembrolizumab
timeFrame: Predose Cycle 1 Day 1 through Follow Up (up to 6 months)
measure: Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)
timeFrame: Baseline to Measured Progressive Disease (PD) or Start of New Anti-Cancer Therapy (up to 28 months)
measure: Disease Control Rate (DCR): Percentage of Participants With a Best Response of CR, PR or Stable Disease (SD)
timeFrame: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (up to 28 months)
measure: Duration of Response (DoR)
timeFrame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (up to 24 months)
measure: Progression Free Survival (PFS)
timeFrame: Baseline to Measured Progressive Disease or Death Due to Any Cause (up to 28 months)
measure: Overall Survival (OS)
timeFrame: Baseline to Death from Any Cause (up to 35 months)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Herlev
country: Denmark
facility: Herlev and Gentofte Hospital
city: Villejuif Cedex
country: France
facility: Gustave Roussy
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: