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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 6
- 主要终点
- Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
15 milligrams per kilogram (mg/kg) Olaratumab + 200 milligrams (mg) Pembrolizumab - Dose Escalation
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.
干预措施: Olaratumab (Drug)
15 milligrams per kilogram (mg/kg) Olaratumab + 200 milligrams (mg) Pembrolizumab - Dose Escalation
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.
干预措施: Pembrolizumab (KEYTRUDA®) (Drug)
20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Escalation
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.
干预措施: Olaratumab (Drug)
20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Escalation
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.
干预措施: Pembrolizumab (KEYTRUDA®) (Drug)
20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Expansion
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.
干预措施: Olaratumab (Drug)
20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Expansion
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.
干预措施: Pembrolizumab (KEYTRUDA®) (Drug)
结局指标
主要结局
Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)
时间窗: 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
次要结局
- 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)
- 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)
- 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)
- 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))
- 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))
- 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))
- 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))
- Progression Free Survival (PFS)(Baseline to Measured Progressive Disease or Death Due to Any Cause (up to 28 months))
- Overall Survival (OS)(Baseline to Death from Any Cause (up to 35 months))