Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors

Официальное название

Phase 1b/2, Multicenter, Open-label, Dose Escalation and Dose Expansion Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Patients With Advanced KRAS G12C-Mutated Solid Tumors

Обзор

This study is to evaluate the safety, tolerability, and PK profiles of Elironrasib and Daraxonrasib as monotherapies and combination therapy in patients with KRAS G12C-mutated solid tumors.

Подробное описание

This is an open-label, multicenter, Phase 1b/2 study evaluating elironrasib and daraxonrasib, administered as monotherapy and in combination, in patients with advanced KRAS G12C-mutated solid tumors to determine the maximum tolerated dose (MTD), identify the recommended Phase 2 dose and schedule (RP2DS), and preliminarily assess antitumor activity.

The study includes a Phase 1b dose escalation and expansion of combination therapy, followed by a Phase 2 evaluation of the selected RP2DS as monotherapy and combination therapy to further assess safety and antitumor activity.

Вмешательства

• Препарат Elironrasib
  oral tablets
• Препарат Daraxonrasib
  oral tablets

Первичные конечные точки

• Number of patients with adverse events (AEs) in Phase 1b [Срок оценки: Up to approximately 3 years]
• Changes in vital signs in Phase 1b [Срок оценки: Up to approximately 3 years]
• Changes in clinical laboratory test values in Phase 1b [Срок оценки: Up to approximately 3 years]
• Dose Limiting Toxicities in Phase 1b [Срок оценки: 21 days]
• Changes in ECGs in Phase 1b [Срок оценки: Up to approximately 3 years]
• Overall Response Rate (ORR) in Phase 2 [Срок оценки: Up to approximately 3 years]

Вторичные конечные точки (12)

• Maximum Observed Blood Concentration of Elironrasib and Daraxonrasib [Срок оценки: up to 21 weeks]
• Time to Reach Maximum Blood Concentration of Elironrasib and Daraxonrasib [Срок оценки: up to 21 weeks]
• Area Under Blood Concentration Time Curve of Elironrasib and Daraxonrasib [Срок оценки: up to 21 weeks]
• Elimination Half-Life of Elironrasib and Daraxonrasib [Срок оценки: up to 21 weeks]
• Ratio of accumulation of Elironrasib and Daraxonrasib from a single dose to steady state with repeated dosing [Срок оценки: up to 21 weeks]
• Overall Response Rate (ORR) in Phase 1b [Срок оценки: Up to approximately 3 years]
• Duration of Response (DOR) [Срок оценки: Up to approximately 3 years]
• Disease Control Rate in Phase 1b [Срок оценки: Up to approximately 3 years]
• Time to Response (TTR) in Phase 1b [Срок оценки: Up to approximately 3 years]
• Progression-Free Survival (PFS) [Срок оценки: Up to approximately 3 years]
• Number of patients with AEs in Phase 2 [Срок оценки: Up to approximately 3 years]
• Changes in vital signs in Phase 2 [Срок оценки: Up to approximately 3 years]

Критерии участия

Критерии включения

• 18 years of age
• Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy

• Phase 1b Dose Escalation: solid tumors, previously treated
• Phase 1b Dose Expansion and Phase 2:

i. NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors ii. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors.

• ECOG performance status 0 or 1
• Adequate organ function

Критерии исключения

• Primary central nervous system (CNS) tumors
• Active brain metastases
• Known impairment of GI function that would alter the absorption
• Major surgical procedures within 28 days or non-study related minor procedures within 7 days of treatment

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 · 23 центра

• City of Hope — Duarte
• UC IRVINE Health — Orange
• UC Davis Comprehensive Cancer Center — Sacramento
• Stanford Cancer Institute — Stanford
• University of Colorado Cancer Center — Aurora
• Florida Cancer Specialists — Sarasota
• Moffitt Cancer Center and Research Institute — Tampa
• Community Health Network — Indianapolis
• … и ещё 15 центров

Испания · 11 центров

• START Barcelona - Hospital HM Nou Delfos — Barcelona
• Institut Catala d'Oncologia Hospital — Barcelona
• University Clinic of Navarra — Madrid
• Fundacion MD Anderson Cancer Center — Madrid
• START Madrid — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• NEXT Oncology - Quirónsalud Madrid University Hospital — Madrid
• University Clinic of Navarra — Pamplona
• … и ещё 3 центра

Франция · 8 центров

• West Cancer Institute — Angers
• Institut Bergonie — Bordeaux
• Hospital Louise Pradel — Bron
• Oscar Lambret Center of Lillle — Lille
• Centre Leon Berard — Lyon
• Cancer Institute of Montpellier — Montpellier
• CHU Nantes — Nantes
• Institute of Cancer of Strasbourg — Strasbourg

Италия · 7 центров

• Department of Medical Oncology - Azienda Ospedaliero Uniersitaria delle Marche — Ancona
• Centro Di Riferimento Oncologico — Aviano
• Institute Romagnolo per lo Studio Tumori — Meldola
• Niguarda Cancer Center — Milan
• Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale" — Naples
• San Luigi Hospital — Orbassano
• AUSL Romagna - S.M. delle Croci Hospital — Ravenna

Германия · 4 центра

• Universitäts Klinikum Köln — Cologne
• Klinikum Esslingen GmbH — Esslingen am Neckar
• Krankenhaus Bethanien Moers — Moers
• Klinkum Nurnberg Paracelsus Medical Unviersity — Nuremberg

Нидерланды · 1 центр

• Netherlands Cancer Institute Antoni van Leeuwenhoek — Amsterdam

Пуэрто-Рико · 1 центр

• Pan American Center for Oncology Trials — San Juan

Публикации

• Cregg J, Edwards AV, Chang S, Lee BJ, Knox JE, Tomlinson ACA, Marquez A, Liu Y, Freilich R, Aay N, Wang Y, Jiang L, Jiang J, Wang Z, Flagella M, Wildes D, Smith JAM, Singh M, Wang Z, Gill AL, Koltun ES. Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers. J PMID 40056080

Идентификаторы

NCT: NCT06128551 · RMC-6291-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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