A Study of MUC16-Directed Antibody Drug Conjugate HWK-016 in Participants With Advanced Solid Tumors.

Официальное название

A Phase 1 First-in-Human Study of MUC16-Directed Antibody Drug Conjugate HWK-016 in Participants With Advanced Solid Tumors.

Обзор

HWK-016-101 is a multicenter, open-label, first-in-human (FIH) Phase 1 study evaluating HWK-016, a targeted antibody-drug conjugate (ADC) in adult participants with advanced or metastatic solid tumors. The study employs a dose escalation and dose expansion design without a control group. The study consists of 2 parts (Part A: monotherapy and Part B: combination therapy with bevacizumab); each part has 2 phases, Phase 1a (dose escalation) and Phase 1b (dose expansion). Enrollment to Part A (Phase 1a and Phase 1b) will include ovarian and endometrial cancers. Enrollment to Part B (Phase 1a and Phase 1b) will include ovarian cancer only. A subsequent protocol amendment may evaluate additional tumor types.

Подробное описание

HWK-016-101 is a Phase 1 study evaluating HWK-016, a mucin-16 (MUC-16) targeted antibody-drug conjugate (ADC) in adult participants with advanced or metastatic solid tumors.

Вмешательства

• Препарат HWK-016, MUCIN-16-targeted ADC
  HWK-016 is a MUCIN-16-targeted Antibody-Drug-Conjugate (ADC) being developed for the treatment of solid tumors.
• Препарат Bevacizumab
  Bevacizumab administered according to the USPI in 21-day cycles

Первичные конечные точки

• Determine Maximum Tolerated Dose (MTD) [Срок оценки: From Cycle 1, Day 1 Until Cycle 1, Day 21 (21-day cycles)]
• Determine Maximum Administered Dose (MAD) [Срок оценки: From Cycle 1, Day 1 to Cycle 1, Day 21 (21-day cycles) until the MTD is reached.]
• Determine Recommended Dose For Expansion (RDE) [Срок оценки: From Cycle 1, Day 1 to Cycle 1, Day 21 (21-day cycle) until MTD is identified.]

Вторичные конечные точки (12)

• Characterize the Volume of Distribution (Vd) of HWK-016 (ADC, total antibody, CPT116, and CPT119) [Срок оценки: Cycle 1 and Cycle 4 (21-day cycles)]
• Maximum Concentration - Cmax of HWK-016 (ADC, total antibody, CPT116, and CPT119) [Срок оценки: At Cycle 1 and Cycle 4 - (21-day cycles)]
• Time to Maximum Concentration (Tmax) of HWK-016 (ADC, total antibody, CPT116, and CPT119) [Срок оценки: Cycle 1 and Cycle 4 - (21-day cycles)]
• Area Under the Concentration Time Curve (AUC) for HWK-016 (ADC, total antibody, CPT116, and CPT119) [Срок оценки: Cycle 1 and Cycle 4 - (21-day cycles]
• T1/2 - Half-life of HWK-016 (ADC, total antibody, CPT116, and CPT119) [Срок оценки: Cycle 1 and Cycle 4 - (21-day cycles)]
• Clearance (CL) [Срок оценки: Cycle 1 and Cycle 4 (21-day cycles)]
• Assess ADA (Anti drug antibody) against HWK-016 [Срок оценки: Every cycle from Cycle 1, Day 1 (21-day cycles) until 30 days past the last dose of study drug for up to 24 months.]
• Evaluate the Overall Response Rate (ORR [Срок оценки: From Cycle 1, Day 1 (21-day cycles), every 6-weeks for the first 4 assessments and then every 6 weeks for up to 24 months until disease progression or 24 months, whichever comes first.]
• Evaluate Overall Survival (OS). [Срок оценки: From Cycle 1, Day 1 (21-day cycles) until death or 24 months, whichever comes first.]
• Evaluate the Duration of Response (DoR) to HWK-016 [Срок оценки: From Cycle 1, Day 1 (21-day cycles) until disease progression or 24 months, whichever comes first.]
• Evaluate Progression-free Survival (PFS) [Срок оценки: From Cycle 1, Day 1 (21-day cycles) infusion to End of Study (up to 24 months)]
• Evaluate Disease control Rate (DCR) [Срок оценки: From Cycle 1, Day 1 (21-day cycles) infusion to End of Study (up to 24 months]

Критерии участия

Критерии включения

• Have one of the following solid tumor cancers:

• Monotherapy escalation, backfill and expansion cohorts:

• Endometrial Carcinoma
• Ovarian Cancer
• Combination Escalation, Backfill and Expansion Cohorts a. Ovarian Cancer

Критерии исключения

• Individual with known or suspected uncontrolled central nervous system (CNS) metastases
• Individual with history of carcinomatous meningitis
• Individual with active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
• Individual with evidence of corneal keratopathy or history of cornea transplant
• Any serious unresolved toxicities from prior therapy
• Significant cardiovascular disease
• Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 milliseconds (ms)
• History of pneumonitis/interstitial lung disease
• Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention

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 · 12 центров

• University of Arkansas - Winthrop P. Rockefeller Cancer Institute — Little Rock
• START - Los Angeles — Los Angeles
• SCRI - Florida Cancer Specialists — Sarasota
• St. Francis Medical Center (OSF Healthcare) — Peoria
• Karmanos Cancer Center — Detroit
• Start - Ny — Lake Success
• Memorial Sloan Kettering Cancer Center — New York
• Atrium Health - Wake Forest — Charlotte
• … и ещё 4 центра

Идентификаторы

NCT: NCT07470853 · HWK-016-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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