A Study of Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)

Официальное название

A Phase 1/2 Study of the Highly Selective ROS1 Inhibitor Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors (ARROS-1)

Обзор

Phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of zidesamtinib (NVL-520), determine the recommended phase 2 dose (RP2D), and evaluate the antitumor activity in patients with advanced ROS1-positive (ROS1+) NSCLC and other advanced ROS1-positive solid tumors. Phase 1 will determine the RP2D and, if applicable, the maximum tolerated dose (MTD) of zidesamtinib in patients with advanced ROS1-positive solid tumors. Phase 2 will determine the objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) of zidesamtinib at the RP2D. Secondary objectives will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and clinical benefit rate (CBR) of zidesamtinib in patients with advanced ROS1-positive NSCLC and other solid tumors.

Подробное описание

In Phase 2, study patients will be enrolled into 5 distinct expansion cohorts:

* Cohort 2a: ROS1-positive NSCLC naïve to Tyrosine Kinase Inhibitor (TKI) therapy and up to 1 prior chemotherapy and/or immunotherapy. * Cohort 2b: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy. * Cohort 2c: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy. * Cohort 2d: ROS1-positive NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy. * Cohort 2e: ROS1-positive solid tumor and progressed on any prior therapy.

Вмешательства

• Препарат Zidesamtinib (NVL-520)
  Oral tablet of zidesamtinib (NVL-520)

Первичные конечные точки

• Maximum Tolerated Dose (MTD) (Phase 1) [Срок оценки: Within 28 days of last patient dosed during dose escalation]
• Recommended Phase 2 Dose (RP2D) [Срок оценки: Within 28 days of last patient dosed during dose escalation.]
• Objective Response Rate (ORR) (Phase 2) [Срок оценки: 2-3 years after first patient dosed.]

Вторичные конечные точки (12)

• Number of participants with treatment-emergent adverse events, as assessed by CTCAE, v5.0 [Срок оценки: Approximately 3 years.]
• Maximum plasma concentration (Cmax) of NVL-520 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Plasma concentration at the end of the dosing interval (Ctau) of NVL-520 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Average plasma concentration (Cavg) of NVL-520 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Time of maximum concentration (Tmax) of NVL-520 [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-520 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Area under the curve from time 0 to 24 (AUC0-24) of NVL-520 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Area under the curve from time 0 to infinity (AUCinf) of NVL-520 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Oral clearance (CL/F) of NVL-520 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Volume of distribution (Vz/F) of NVL-520 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Half-life (t1/2) of NVL-520 [Срок оценки: Pre-dose and up to 24 hours post-dose]
• Objective response rate (ORR) [Срок оценки: 2-3 years after first patient dosed]

Критерии участия

Критерии включения

• Age ≥18 years (Cohort 2e only: Age ≥12 years).
• Disease Criteria:

• Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement.
• Phase 2: Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangement.
• Phase 2: Cohort 2e: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (other than NSCLC) with ROS1 rearrangement.
• Prior anticancer treatment (except cohort 2a).
• Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.1. Phase 2: Must have measurable disease according to RECIST 1.1.
• Adequate baseline organ function and bone marrow reserve.

Критерии исключения

• Patient's cancer has a known oncogenic driver alteration other than ROS1.
• Known allergy/hypersensitivity to excipients of NVL-520.
• Major surgery within 4 weeks of first dose of study drug.
• Ongoing 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 · 20 центров

• UCI Medical Center — Orange
• Stanford Medicine — Palo Alto
• UC Davis Comprehensive Cancer Center — Sacramento
• University of Colorado Cancer Center — Denver
• Georgetown University Medical Center — Washington D.C.
• University of Miami — Coral Gables
• University of Chicago — Chicago
• Mass General Hospital — Boston
• … и ещё 12 центров

Италия · 7 центров

• Università Politecnica Marche — Ancona
• IRCCS Istituto Tumori Giovanni Paolo II — Bari
• Istituto Europeo di Oncologia — Milan
• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan
• Istituto Oncologico Veneto — Padova
• Ospedale Santa Maria delle Croci — Ravenna
• Istituto Nazionale Tumori Regina Elena — Rome

Япония · 7 центров

• Kanagawa Cancer Center — Kanagawa
• Okayama University Hospital — Okayama
• Kindai University Hospital — Osaka
• Shizuoka Cancer Center — Shizuoka
• National Cancer Center Hospital — Tokyo
• The Cancer Institute Hospital Of JFCR — Tokyo
• Wakayama Medical University Hospital — Wakayama

Испания · 6 центров

• University Hospital of A Coruña — A Coruña
• UOMI Cancer Center - Clinica Tres Torres — Barcelona
• Vall d'Hebron University Hospital — Barcelona
• Gregorio Marañón Hospital — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitario HM Sanchinarro — Madrid

Франция · 4 центра

• Centre Legon Berard — Lyon
• CHU de Nantes — Nantes
• Claudius Regaud Institute — Toulouse
• Institute Gustave Roussy — Villejuif

South Korea · 4 центра

• National Cancer Center — Gyeonggi-do
• Seoul National University Hospital — Seoul
• Yonsei University Health System — Seoul
• Samsung Medical Center — Seoul

Тайвань · 3 центра

• Chung Shan Medical University Hospital — Taichung
• National Cheng Kung University Hospital — Tainan
• National Taiwan University Hospital — Taipei

Австралия · 2 центра

• Chris O'Brien Lifehouse — Camperdown
• Peter MacCallum Cancer Centre — Melbourne

Канада · 2 центра

• Cross Cancer Institute — Edmonton
• Princess Margaret Cancer Research — Toronto

Нидерланды · 2 центра

• Netherlands Cancer Institute — Amsterdam
• University Medical Centre Groningen — Groningen

Сингапур · 2 центра

• National University Hospital Singapore — Singapore
• National Cancer Centre Singapore — Singapore

Великобритания · 2 центра

• Royal Marsden Hospital — London
• Christie NHS Foundation Trust — Manchester

Бельгия · 1 центр

• University Hospital Leuven — Leuven

Германия · 1 центр

• Cologne University Hospital — Cologne

Идентификаторы

NCT: NCT05118789 · NVL-520-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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