A Study of NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1)

Официальное название

A Phase 1a/1b Study of the Selective Tyrosine Kinase Inhibitor NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1)

Обзор

Phase 1a/1b dose escalation and expansion study designed to evaluate the safety and tolerability of NVL-330, determine the recommended Phase 2 dose (RP2D), and evaluate the antitumor activity in participants with advanced or metastatic human epidermal growth factor receptor 2 (HER2) -altered non-small lung cancer (NSCLC). Phase 1a dose escalation is designed to assess the safety and tolerability of NVL-330 and to select the candidate RP2D(s) and, if applicable, the MTD. Phase 1b expansion is designed to further evaluate the overall safety and tolerability of the candidate RP2D(s) of NVL-330 and to determine the RP2D of NVL-330 in participants with advanced or metastatic HER2 mutant NSCLC.

Подробное описание

The planned Phase 1a/1b first-in-human study is designed as a two-part clinical trial to investigate NVL-330 in pre-treated participants with advanced or metastatic HER2-altered NSCLC. The dose escalation phase of the trial is designed to enroll a set number of participants per cohort at protocol defined dose levels.

After the initial participants are treated at a given dose level and monitored for at least 28 days, available data will be reviewed, and initiation of the next dosing group will proceed with consideration given to the overall safety profile.

The expansion phase of the trial is designed to further evaluate safety and activity and to confirm the RP2D(s).

Вмешательства

• Препарат NVL-330
  Oral Tablet of NVL-330

Первичные конечные точки

• Recommended Phase 2 Dose (RP2D) [Срок оценки: As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)]
• Maximum Tolerated Dose (MTD) [Срок оценки: As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)]
• Incidence and severity of Treatment Emergent Adverse Events (TEAEs) [Срок оценки: First dose of study drug through 30 days after the last dose of study drug]

Вторичные конечные точки (12)

• Effect of Food on Maximum Plasma Concentration (Cmax) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Effect of Food on Area Under the Curve from Time 0 to 24 (AUC0-24) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Effect of Food on Area Under the Curve from Time 0 to Infinity (AUCinf) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Effect of Food on Time of Maximum Concentration (Tmax) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Maximum plasma concentration (Cmax) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Maximum plasma concentration (Cmax- dose normalized) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Plasma concentration at the end of the dosing interval (Ctau) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Plasma concentration 24 hours post-dose (C24) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Average plasma concentration (Cavg) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Time of maximum concentration (Tmax) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Area Under the Curve at the End of the Dosing Interval (AUCtau) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Area Under the Curve at the End of the Dosing Interval (AUCtau - dose normalized) of NVL-330 [Срок оценки: Pre-dose and up to 24 hours post-dose]

Критерии участия

Критерии включения

• Age ≥ 18 years
• Histologically or cytologically confirmed locally advanced or metastatic NSCLC
• Documented HER2 status as follows:

• Phase 1a: Documented oncogenic HER2 mutation such as HER2 exon20 insertion mutations or single nucleotide variants or HER2 amplification.
• Phase 1b: Documented oncogenic HER2 mutation.
• Identification of lesions as follows:

• Phase 1a: Must have evaluable disease (target or nontarget) according to RECIST 1.1.
• Phase 1b: Must have measurable disease, defined as ≥ 1 radiologically measurable target lesion according to RECIST 1.1.
• Adequate organ function and bone marrow reserve

Критерии исключения

• Participant's cancer has known oncogenic driver alteration other than HER2
• Known allergy/hypersensitivity to excipients of NVL-330
• Major surgery within 4 weeks of the first dose of study drug
• Ongoing or recent anticancer therapy
• Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study

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 · 17 центров

• City of Hope - Lennar — Irvine
• University of California, Davis Comprehensive Cancer Center — Sacramento
• Stanford Cancer Institute — Stanford
• Sarah Cannon Research Institute at HealthONE — Denver
• Georgetown University Medical Center — Washington D.C.
• Sibley Memorial Hospital — Washington D.C.
• Sylvester Comprehensive Cancer Center — Miami
• Johns Hopkins Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Bayview Medical C — Baltimore
• … и ещё 9 центров

Австралия · 2 центра

• Chris O'Brien Lifehouse — Camperdown
• North Shore Health Hub — Saint Leonards

Канада · 2 центра

• Cross Cancer Institute — Edmonton
• Princess Margaret Cancer Center - University Health Network — Toronto

Идентификаторы

NCT: NCT06521554 · NVL-330-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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