Phase 1/2 Study of PYX-201 in Combination With Pembrolizumab in Advanced Solid Tumors

Официальное название

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

Обзор

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.

Вмешательства

• Препарат PYX-201
  Intravenous (IV) infusion.
• Препарат pembrolizumab
  IV infusion.

Первичные конечные точки

• Number of Participants who Experience a Dose-Limiting Toxicity (DLT) [Срок оценки: Day 1 to Day 21]
• Number of Participants who Experience an Adverse Event (AE) [Срок оценки: Up to approximately 2 years]
• Number of Participants who Experience Clinically Significant Changes in Clinical Laboratory Parameters [Срок оценки: Up to approximately 2 years]
• Number of Participants who Experience Clinically Significant Changes in Vital Signs [Срок оценки: Up to approximately 2 years]
• Number of Participants who Experience Clinically Significant Changes in electrocardiogram (ECG) Parameters [Срок оценки: Up to approximately 2 years]

Вторичные конечные точки (12)

• Objective Response Rate (ORR) [Срок оценки: Day 1 up to approximately 2 years]
• Duration of Response (DOR) [Срок оценки: Day 1 up to approximately 2 years]
• Disease Control Rate (DCR) [Срок оценки: Day 1 up to approximately 2 years]
• Time to Response [Срок оценки: Day 1 up to approximately 2 years]
• Clinical Benefit Rate (CBR) [Срок оценки: Day 1 up to approximately 2 years]
• Maximum Observed Concentration (Cmax) of PYX-201 [Срок оценки: Day 1 up to approximately 2 years]
• Time to Maximum Concentration (Tmax) of PYX-201 [Срок оценки: Day 1 up to approximately 2 years]
• Clearance (CL) of PYX-201 [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 [Срок оценки: Day 1 up to approximately 2 years]
• Area Under the Concentration-time Curve Over the Dosing Interval (AUCtau) of PYX-201 [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 [Срок оценки: Day 1 up to approximately 2 years]
• Half-Life (t½) for Antibody-drug Conjugate (ADC) [Срок оценки: Day 1 up to approximately 2 years]

Критерии участия

Критерии включения

• 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 1.
• 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.

Критерии исключения

• 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.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 11 центров

• University of California San Diego — San Diego
• Sarcoma Oncology Center — Santa Monica
• Moffitt Cancer Center — Tampa
• University of Chicago — Chicago
• Massachusetts General Hospital — Boston
• Dana-Farber Cancer Institute — Boston
• University of Pennsylvania — Philadelphia
• University of Pittsburgh Medical Center — Pittsburgh
• … и ещё 3 центра

Испания · 5 центров

• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital Universitario Ramón y Cajal — Madrid
• START Madrid - Hospital Universitario Fundación Jiménez Díaz — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Clínico Universitario de Valencia — Valencia

Франция · 3 центра

• Hopital Saint - Andre - CHU de Bordeaux — Bordeaux
• Centre Léon Bérard — Lyon
• Hôpital de la Timone — Marseille

Идентификаторы

NCT: NCT06795412 · PYX-201-102 · KEYNOTE-G17 · MK-3475-G17 · 2025-521828-30-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗