A Study of PYX-201 in Advanced Solid Tumors

Официальное название

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

Обзор

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.

Вмешательства

• Препарат PYX-201
  Antibody-Drug Conjugate

Первичные конечные точки

• Number of Participants who Experience a Dose-limiting Toxicity (DLT) in Dose Escalation [Срок оценки: Day 1 to Day 21]
• Safety and Tolerability as assessed by adverse event monitoring for participants in Dose Escalation [Срок оценки: Up to approximately 3 years]
• Objective Response Rate (ORR) observed in participants in Dose Expansion [Срок оценки: Up to approximately 2 years]

Вторичные конечные точки (12)

• Maximum Observed Concentration (Cmax) of PYX-201 in Dose Escalation and Dose Expansion [Срок оценки: Day 1 up to approximately 2 years]
• Time to Maximum Concentration (Tmax) of PYX-201 in Dose Escalation and Dose Expansion [Срок оценки: Day 1 up to approximately 2 years]
• Clearance (CL) of PYX-201 in Dose Escalation [Срок оценки: 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 [Срок оценки: Day 1 up to approximately 2 years]
• Area Under the Concentration-time Curve Over the Dosing Interval (AUCtau) of PYX-201 in Dose Escalation [Срок оценки: 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 [Срок оценки: Day 1 up to approximately 2 years]
• Half-life (t½) of PYX-201 in Dose Escalation [Срок оценки: Day 1 up to approximately 2 years]
• Objective Response Rate (ORR) observed in participants in Dose Escalation [Срок оценки: Up to approximately 3 years]
• Duration of Response (DOR) observed in participants in Dose Escalation and Dose Expansion [Срок оценки: Up to approximately 3 years]
• Progression-free Survival (PFS) observed in participants in Dose Escalation [Срок оценки: Up to approximately 3 years]
• Disease Control Rate (DCR) observed in participants in Dose Escalation and Dose Expansion [Срок оценки: Up to approximately 3 years]
• Time to Response (TTR) observed in participants in Dose Escalation and Dose Expansion [Срок оценки: Up to approximately 3 years]

Критерии участия

Inclusion

• 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 1.
• Participant must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• 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.

Exclusion

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 17 центров

• HonorHealth Research Institute — Scottsdale
• Ronald Reagan UCLA Medical Center — Los Angeles
• SCRI - HealthOne Denver — Denver
• SCRI - Florida Cancer Specialists — Sarasota
• Winship Cancer Institute, Emory University — Atlanta
• University of Chicago Medicine — Chicago
• Massachusetts General Hospital — Boston
• Dana-Farber Cancer Institute — Boston
• … и ещё 9 центров

Испания · 5 центров

• Hospital Universitari Vall d'Hebrón — Barcelona
• START Madrid - Hospital Universitario Fundación Jiménez Díaz — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitario HM Sanchinarro — Madrid
• Hospital Clínico Universitario de Valencia — Valencia

Бельгия · 4 центра

• Institut Jules Bordet — Brussels
• Cliniques Universitaires Saint-Luc — Brussels
• Universitair Ziekenhuis Antwerpen — Edegem
• Universitair Ziekenhuis Gent — Ghent

Великобритания · 3 центра

• University College Hospital — London
• The Royal Marsden Hospital — London
• Sarah Cannon Research Institute London — London

Идентификаторы

NCT: NCT05720117 · PYX-201-101 · 2023-509687-14-00 · 2022-002284-30

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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