A Phase 1b/2 Study to Evaluate Safety and Clinical Activity of Avelumab in Combination With Bempegaldesleukin(NKTR-214) With or Without Talazoparib or Enzalutamide in Participants With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 3
- 试验地点
- 5
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLT)
研究概览
简要总结
Evaluation of the combination of avelumab + bempegaldesleukin (NKTR-214 ) in locally advanced squamous cell carcinoma of the head and neck ( metastatic SCCHN) and avelumab + bempegaldesleukin (NKTR-214) + talazoparib or enzalutamide in metastatic castration resistant prostate cancer (mCRPC).
详细描述
Phase 1b/ Phase 2 Design
Phase 1b will be the sequential dose-finding study.
Once the Phase 1b component is completed, Phase 2 will be initiated to further evaluate the safety and anti-tumor activity across combinations of therapy.
Combination A will enroll participants with SCCHN.
Combination B and C will enroll participants with mCRPC
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
- •Participants must be ≥ 18 years old.
- •Participants with SCCHN or mCRCP.
- •Participants must have histological diagnosis of solid tumors and provide tumor tissue.
- •Measurable disease by RECIST v1.1 with at least 1 measurable lesion.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or
- •Adequate bone marrow, renal and liver function
- •Highly effective contraceptive use by men with the ability to father a child or women of childbearing potential.
- •A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) at C1D
- •Signed and dated informed consent.
排除标准
- •Known prior severe hypersensitivity to investigational products or any component in their formulations, including known severe hypersensitivity reactions to monocolonal antibodies.
- •Known history of: immune-mediated colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis.
- •Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
- •Prior organ transplantation including allogenic stem cell transplantation.
- •Vaccination within 4 weeks prior to C1D1 and while on trial is prohibited except for administration of inactivated vaccines.
- •Known symptomatic brain lesions requiring steroids.
- •Known history of testing positive for human immunodeficiency virus (HIV or known acquired immunodeficiency syndrome (AIDS).
- •Positive HBV surface antigen or HCV test indicating acute or chronic infection..
- •Active infection requiring systemic therapy
- •Clinically significant (i.e., active) cardiovascular disease including the following: documented left ventricular ejection fraction (LVEF) <50% by ECHO/MUGA; cerebral vascular accident/stroke or transient ischemic attack; myocardial infarction; unstable angina; congestive heart failure or serious cardiac arrhythmia (uncontrolled, clinically significant) requiring medication.
- •Diagnosis of any other malignancy within 2 years prior to C1D1, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix and for Combination A only, low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (e.g., surgery, radiation, or castration) or adequately treated prostate cancer.
- •Current use of immunosuppressive medication at the time of study enrollment.
- •Major surgery within 4 weeks prior to study enrollment.
- •Conditions that may impair intake or absorption such as inability to swallow capsules or tablets; known malabsorption syndrome; or baseline diarrhea ≤ Grade
- •Participation in other studies involving investigational drug(s) within 2 weeks prior to C1D1.
研究组 & 干预措施
Combination A
Avelumab + Bempegaldesleukin (NKTR-214) for treatment of locally recurrent (not amendable for treatment with curative intent) or metastatic squamous cell carcinoma of the head and neck
干预措施: avelumab (Drug)
Combination A
Avelumab + Bempegaldesleukin (NKTR-214) for treatment of locally recurrent (not amendable for treatment with curative intent) or metastatic squamous cell carcinoma of the head and neck
干预措施: Bempegaldesleukin (Drug)
Combination B
Avelumab + Bempegaldesleukin (NKTR-214) + Talazoparib for treatment of metastatic castration-resistant prostate cancer (mCRPC). Phase 2 will focus on enrolling participants with DDR defect positive mCRPC.
干预措施: avelumab (Drug)
Combination B
Avelumab + Bempegaldesleukin (NKTR-214) + Talazoparib for treatment of metastatic castration-resistant prostate cancer (mCRPC). Phase 2 will focus on enrolling participants with DDR defect positive mCRPC.
干预措施: Bempegaldesleukin (Drug)
Combination B
Avelumab + Bempegaldesleukin (NKTR-214) + Talazoparib for treatment of metastatic castration-resistant prostate cancer (mCRPC). Phase 2 will focus on enrolling participants with DDR defect positive mCRPC.
干预措施: talazoparib (Drug)
Combination C
Combination C: Avelumab + Bempegaldesleukin (NKTR-214) + Enzalutamide for Treatment of mCRPC
干预措施: avelumab (Drug)
Combination C
Combination C: Avelumab + Bempegaldesleukin (NKTR-214) + Enzalutamide for Treatment of mCRPC
干预措施: Bempegaldesleukin (Drug)
Combination C
Combination C: Avelumab + Bempegaldesleukin (NKTR-214) + Enzalutamide for Treatment of mCRPC
干预措施: enzalutamide (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLT)
时间窗: Cycle 1 of the treatment period (28 days)
DLTs were graded according to NCI- CTCAE version 4.03 and coded using the latest version of Medical Dictionary for Regulatory Activities (MedDRA) preferred term (PT) as event category and MedDRA primary system organ class (SOC) body term as Body System category.
次要结局
- Time to Tumor Response (TTR)(Approximately 8 months (246 days).)
- Progression-Free Survival (PFS)(Approximately 8 months (246 days).)
- Pharmacokinetic (PK) Parameters - Cmax and Ctrough for Avelumab and NKTR-214(Blood samples were collected on Day 1 and Day 15 in Cycle 1 and Cycle 2 for avelumab. Blood samples were collected on Day 1, Day 3, Day 4 and Day 8 in Cycle 1, Day1 and Day 8 in Cycle 2 for NKTR-214.)
- Number of Participants With Treatment-Emergent Adverse Events(TEAEs), Serious TEAEs, TEAEs Leading to Death and Infusion-Related Reactions (IRRs) During On-treatment Period(Approximately 6 months (190 days))
- Duration of Response (DR)(Approximately 8 months (246 days).)
- Number of Participants With Positive Anti-Drug Antibody (ADA) Results(Day 1 of Cycle 1, 2 and end of treatment (EOT).)
- Number of Participants With Positive Neutralizing Antibody (nAb) Results(Day 1 of Cycle 1, 2 and EOT)
- PD-L1 Expression Level in Baseline and On-treatment Tumor Tissue(On-treatment biopsy is required to be collected on Cycle 1 between Days 9 and 14 for participants in Combination A.)
- Number of Participants With Laboratory Abnormalities With NCI-CTCAE Grade >= 3 - Safety Analysis Set(Day 1, Day 15 of each treatment cycle)
- Overall Survival (OS)(Approximately 8 months (246 days).)