NCT05720117招募中1 期
A First-in-Human, Open-label, Multicenter, Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PYX-201 in Participants With Advanced Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 330
- 试验地点
- 43
- 主要终点
- Number of Participants who Experience a Dose-limiting Toxicity (DLT) in Dose Escalation
研究概览
简要总结
The primary objectives of this study are to determine the recommended dose(s) of PYX-201 for participants with recurrent/metastatic (R/M) solid tumors, and to determine the objective response rate (ORR) in participants treated with PYX-201 as a single agent.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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 solid tumors including locally advanced/metastatic HR+ and HER2- breast cancer (post CDK4/6 inhibitor +/- ET, ≤ 2 lines systemic therapy), TNBC (1-3 prior lines including post ADC topo-1 payload), HNSCC (1-2 prior lines including post PD-L1/PD1 and platinum based therapy), and other solid tumor types (≤ 2 lines systemic therapy).
- •Male or non-pregnant, non-lactating female participants age ≥18 years.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to
- •Participant must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Life expectancy of >3 months, in the opinion of the Investigator.
- •Corrected QTcF <470 msec.
- •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.
- •History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; in situ cervical carcinoma; adequately treated, noninvasive bladder cancer.
- •Known symptomatic brain metastases.
- •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 Grade ≤1 NCI-CTCAE v5.0 from acute non-hematologic toxicity.
- •Participants with NCI-CTCAE v5.0 Grade >1 neuropathy of any etiology.
- •Prior solid organ or bone marrow progenitor cell transplantation.
- •Prior high-dose chemotherapy requiring stem cell rescue.
- •Received systemic anticancer therapy within 28 days or within 5 half-lives (whichever is shorter) prior to the start of study drug.
- •Palliative radiation therapy within 14 days prior to the start of study drug.
- •Previously received extra domain B splice variant of fibronectin (EDB+FN) targeting treatments at any time prior to the start of PYX-201 treatment.
- •History of uncontrolled diabetes mellitus.
- •History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
- •Participants with corneal epithelial disease, with the exception of mild punctate keratopathy
- •Participants with the best-corrected visual acuity in the worst-seeing eye worse than 20/100 (Snellen equivalent).
- •Participants with a history of (noninfectious) pneumonitis/ interstitial lung disease that required steroids, has current pneumonitis/ interstitial lung disease, or evidence of active pneumonitis on screening chest CT scan or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
排除标准
- 未提供
研究组 & 干预措施
Dose Expansion Cohort A (HNSCC)
Experimental
干预措施: PYX-201 (Drug)
Dose Expansion Cohort B (TNBC)
Experimental
干预措施: PYX-201 (Drug)
Dose Escalation
Experimental
干预措施: PYX-201 (Drug)
Dose Expansion Cohort C (HR+ HER2- BC)
Experimental
干预措施: PYX-201 (Drug)
Dose Expansion Cohort D (Other Solid Tumor Types)
Experimental
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) in Dose Escalation
时间窗: Day 1 to Day 21
DLT is defined as (1) an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs after the treatment with PYX-201 and (2) meets any of the predefined criteria outlined in the protocol.
Safety and Tolerability as assessed by adverse event monitoring for participants in Dose Escalation
时间窗: Up to approximately 3 years
Adverse Events as characterized by type, incidence, seriousness, relationship to study treatment, timing, and severity (as graded by NCI-CTCAE Version 5.0). Any clinically significant changes in clinical laboratory parameters, vital signs, and electrocardiogram (ECG) parameters will be recorded as AEs.
Objective Response Rate (ORR) observed in participants in Dose Expansion
时间窗: Up to approximately 2 years
次要结局
- Clearance (CL) of PYX-201 in Dose Escalation(Day 1 up to approximately 2 years)
- Maximum Observed Concentration (Cmax) of PYX-201 in Dose Escalation and Dose Expansion(Day 1 up to approximately 2 years)
- Time to Maximum Concentration (Tmax) of PYX-201 in Dose Escalation and Dose Expansion(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 in Dose Escalation(Day 1 up to approximately 2 years)
- Area Under the Concentration-time Curve Over the Dosing Interval (AUCtau) of PYX-201 in Dose Escalation(Day 1 up to approximately 2 years)
- Area Under the Concentration-time Curve from Time 0 Extrapolated to Infinity (AUC0-inf) of PYX-201 in Dose Escalation(Day 1 up to approximately 2 years)
- Half-life (t½) of PYX-201 in Dose Escalation(Day 1 up to approximately 2 years)
- Objective Response Rate (ORR) observed in participants in Dose Escalation(Up to approximately 3 years)
- Duration of Response (DOR) observed in participants in Dose Escalation and Dose Expansion(Up to approximately 3 years)
- Progression-free Survival (PFS) observed in participants in Dose Escalation(Up to approximately 3 years)
- Disease Control Rate (DCR) observed in participants in Dose Escalation and Dose Expansion(Up to approximately 3 years)
- Time to Response (TTR) observed in participants in Dose Escalation and Dose Expansion(Up to approximately 3 years)
- Overall Survival (OS) observed in participants in Dose Escalation(Up to approximately 3 years)
- Incidence of Anti-drug Antibodies (ADA) in participants treated with PYX-201 in Dose Escalation and Dose Expansion(Up to approximately 2 years)
- Clinical Benefit Rate (CBR) observed in participants in Dose Expansion(Up to approximately 2 years)
- Median Progression-free Survival (mPFS) observed in participants in Dose Expansion(Up to approximately 4 years)
- Median Overall Survival (mOS) observed in participants in Dose Expansion(Up to approximately 4 years)
- Cmax of PYX-201 in Dose Expansion(Up to approximately 2 years)
- Tmax of PYX-201 in Dose Expansion(Up to approximately 2 years)
- Trough Concentration of PYX-201 in Dose Expansion(Up to approximately 2 years)
- Safety and Tolerability as assessed by adverse event monitoring for participants in Dose Expansion(Up to approximately 2 years)
研究者
研究点 (43)
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