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

Study Overview
=================
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.

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

Conditions
-----------------
Soft Tissue Sarcoma

Intervention / Treatment
-----------------
* Drug: Olaratumab
* Drug: Pembrolizumab


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olaratumab Dose Level 1 + Pembrolizumab<br>Olaratumab given intravenously (IV) and pembrolizumab given IV. | Drug: Olaratumab<br>* Administered IV<br>* Other names: LY3012207;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|
| Experimental: Olaratumab Dose Level 2 + Pembrolizumab<br>Olaratumab given IV and pembrolizumab given IV. | Drug: Olaratumab<br>* Administered IV<br>* Other names: LY3012207;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|
| Experimental: Olaratumab + Pembrolizumab Expansion<br>Olaratumab given IV and pembrolizumab given IV. | Drug: Olaratumab<br>* Administered IV<br>* Other names: LY3012207;Drug: Pembrolizumab<br>* Administered IV<br>* Other names: MK3475;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| PK: Minimum Serum Concentration (Cmin) of Olaratumab | PK: Cmin of olaratumab | Pre-dose on Day 1 of Cycles 2 and 4 (21 Day Cycles) | 
| PK: Elimination Half-Life of Olaratumab | PK: Elimination half-life of olaratumab | Days 8 to 21 of Cycles 1 and 3 (21 Day Cycles) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) |