A Phase 1/2, Open-label, Global, Multicenter, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PYX-201 in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 28
- 主要终点
- Number of Participants who Experience a Dose-Limiting Toxicity (DLT)
研究概览
简要总结
The primary objective of this study is to determine the recommended Phase 2 doses (RP2D(s)) and maximum tolerated dose (MTD) of PYX-201 in combination with pembrolizumab for participants with advanced solid tumors.
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 or cytologically confirmed advanced solid tumors, including first-line (1L) head and neck squamous cell carcinoma (HNSCC), advanced or metastatic triple negative breast cancer (TNBC), hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative breast cancer (HER2- BC), gastric cancer (GC), cervical cancer, and second-line and higher (2L+) HNSCC.
- •Male or non-pregnant, non-lactating female participants age ≥18 years.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to
- •Participant must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
- •Life expectancy of >3 months, in the opinion of the Investigator.
- •Adequate hematologic function.
- •Adequate hepatic function.
- •Adequate renal function.
- •Adequate coagulation profile.
- •Clinical sites must conduct fresh tumor biopsy or provide participant's archived tumor tissue sample.
排除标准
- •Known additional malignancy that is progressing or has required active treatment within the past 2 years.
- •Have any active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Significant cardiovascular disease within 6 months prior to start of study drug.
- •Evidence of an active systemic bacterial, fungal, or viral infection requiring treatment at the start of study drug.
- •Known active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS).
- •Failure to recover to Baseline severity or National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 Grade ≤1 from acute non-hematologic toxicity due to previous therapy, prior to Screening.
- •Participants with Grade >1 neuropathy of any grade per CTCAE v5.0 and/or receiving treatment for neuropathy at Screening.
- •History of uncontrolled diabetes mellitus.
- •Participants with immunodeficiency or active autoimmune disease that is contraindicated for pembrolizumab.
- •Participants with a history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
- •Prior solid organ or bone marrow progenitor cell transplantation.
- •Prior high-dose chemotherapy requiring stem cell rescue.
- •Previously received treatment with a programmed death-1 (PD-1)/L1 inhibitor any prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor.
- •Severe hypersensitivity (Grade ≥3) to pembrolizumab and/or any of its excipients and/or PYX-201 and/or any of its excipients.
研究组 & 干预措施
Part 2: Dose Expansion
Part 2 dose-expansion cohorts will be opened based on emerging data to further inform the safety, tolerability, and preliminary efficacy determinations as defined.
干预措施: pembrolizumab (Drug)
Part 1: Dose Escalation
Participants will receive escalating doses of PYX-201 to evaluate the safety, tolerability, and preliminary efficacy of PYX-201 in combination with pembrolizumab.
干预措施: PYX-201 (Drug)
Part 1: Dose Escalation
Participants will receive escalating doses of PYX-201 to evaluate the safety, tolerability, and preliminary efficacy of PYX-201 in combination with pembrolizumab.
干预措施: pembrolizumab (Drug)
Part 2: Dose Expansion
Part 2 dose-expansion cohorts will be opened based on emerging data to further inform the safety, tolerability, and preliminary efficacy determinations as defined.
干预措施: PYX-201 (Drug)
结局指标
主要结局
Number of Participants who Experience a Dose-Limiting Toxicity (DLT)
时间窗: Day 1 to Day 21
Number of Participants who Experience Clinically Significant Changes in Clinical Laboratory Parameters
时间窗: Up to approximately 2 years
Number of Participants who Experience an Adverse Event (AE)
时间窗: Up to approximately 2 years
Number of Participants who Experience Clinically Significant Changes in Vital Signs
时间窗: Up to approximately 2 years
Number of Participants who Experience Clinically Significant Changes in electrocardiogram (ECG) Parameters
时间窗: Up to approximately 2 years
次要结局
- Objective Response Rate (ORR)(Day 1 up to approximately 2 years)
- Duration of Response (DOR)(Day 1 up to approximately 2 years)
- Disease Control Rate (DCR)(Day 1 up to approximately 2 years)
- Time to Response(Day 1 up to approximately 2 years)
- Clinical Benefit Rate (CBR)(Day 1 up to approximately 2 years)
- Maximum Observed Concentration (Cmax) of PYX-201(Day 1 up to approximately 2 years)
- Time to Maximum Concentration (Tmax) of PYX-201(Day 1 up to approximately 2 years)
- Clearance (CL) of PYX-201(Day 1 up to approximately 2 years)
- Incidence of Anti-PYX-201 Antibodies(Day 1 up to approximately 2 years)
- Area Under the Concentration-time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-t) of PYX-201(Day 1 up to approximately 2 years)
- Half-Life (t½) for Antibody-drug Conjugate (ADC)(Day 1 up to approximately 2 years)
- Half-Life (t½) for Free Payload(Day 1 up to approximately 2 years)
- Half-Life (t½) for Total Antibody (tAb)(Day 1 up to approximately 2 years)
- Area Under the Concentration-time Curve Over the Dosing Interval (AUCtau) of PYX-201(Day 1 up to approximately 2 years)
- Area Under the Concentration-time Curve from Time 0 Extrapolated to Infinity (AUC0-inf) of PYX-201(Day 1 up to approximately 2 years)