A Phase II Study of Neoadjuvant Opnurasib KRAS G12C Inhibitor in Patients With Surgically Resectable Non-Small Cell Lung Cancer (CCTG IND.242A): A Substudy of the IND.242 Platform Master Protocol.

Autor: Spicer J; McGill University Health Centre (MUHC), Montreal, QC, Canada., Blais N; Centre Hospitalier Universitaire de Montréal (CHUM), Montréal, QC, Canada., Owen S; McGill University Health Centre (MUHC), Montreal, QC, Canada., Robinson AG; Kingston Health Sciences Centre, Kingston, ON, Canada., Chu Q; Cross Cancer Institute, Edmonton, ON, Canada., Labbe C; Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, Canada., Shieh B; McGill University Health Centre (MUHC), Montreal, QC, Canada., Brown-Walker P; Canadian Cancer Trials Group, Kingston, ON, Canada., Sederias J; Canadian Cancer Trials Group, Kingston, ON, Canada., Jensen K; Novartis Healthcare, Copenhagen, Denmark., Farago AF; Novartis Pharmaceuticals, Cambridge, MA, USA., Tsao MS; Princess Margaret Hospital, Toronto, ON, Canada., Cottrell TR; Kingston Health Sciences Centre, Kingston, ON, Canada; Canadian Cancer Trials Group, Kingston, ON, Canada., Kidane B; Cancer Care Manitoba, Winnipeg, MB, Canada., Laurie S; The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada., Juergens R; Juravinski Cancer Centre, Hamilton, ON, Canada., Bradbury PA; Princess Margaret Hospital, Toronto, ON, Canada., Tu W; Canadian Cancer Trials Group, Kingston, ON, Canada., Gaudreau PO; Kingston Health Sciences Centre, Kingston, ON, Canada; Canadian Cancer Trials Group, Kingston, ON, Canada. Electronic address: p-ogaudreau@ctg.queensu.ca.
Jazyk: angličtina
Zdroj: Clinical lung cancer [Clin Lung Cancer] 2024 Sep 20. Date of Electronic Publication: 2024 Sep 20.
DOI: 10.1016/j.cllc.2024.09.003
Abstrakt: Molecularly targeted agents are increasingly being studied in the treatment of early-stage non-small cell lung cancer (NSCLC) to try and improve cure. However, phase 3 data on neoadjuvant therapy have largely been conducted in a biomarker agnostic manner with inconsistent exclusion of EGFR and ALK alterations. Our objective was to develop IND.242 as a large-scale neoadjuvant platform trial to introduce novel agents into the preoperative window for molecularly-defined NSCLC patient populations. Given that KRAS G12C mutations are common in the overall NSCLC patient population, ranging from 9.4% to 13% of cases across different cohorts, and may be associated to worse prognosis, the initial IND.242A Substudy was designed to test neoadjuvant JDQ443 (opnurasib), a selective KRAS G12C inhibitor. This current trial report describes the multicenter, Canadian Cancer Trials Group (CCTG)-led IND.242 neoadjuvant phase 2 platform master protocol and its first Substudy (IND.242A) of neoadjuvant opnurasib KRAS G12C inhibitor for patients with surgically resectable NSCLC (AJCC 8th edition stage IA2 to IIIA). In IND.242A, a maximum of 27 patients will be accrued in participating Canadian sites. The primary objective is the rate of major pathological response (MPR) following neoadjuvant opnurasib. Secondary objectives include safety and tolerability of the treatment regimen, objective response rate (ORR) by RECIST 1.1 for the neoadjuvant treatment period, pathological complete response (pCR) rate, event-free survival (EFS) at 2 years, and surgical outcomes. Exploratory objectives are to explore patient related outcomes (PROs) and identify potential predictive biomarkers of response and mechanisms of resistance on tissue and peripheral blood samples.
Competing Interests: Disclosure The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JS; received speaker fees, honoraria or consulting fees from Merck, AstraZeneca, Bristol Myers Squibb, Roche, Novartis, Amgen, Protalix Biotherapeutics, Xenetic Biosciences, Regeneron, Eisai, Peerview, OncLive, and Medscape; and received research grants from AstraZeneca, Bristol Myers Squibb, Merck, Roche, CLS Therapeutics and Protalix Biotherapeutics. SO; participated in advisory boards for Roche, Novocure, Takeda, Novartis and Bristol Myers Quibb; and has received honoraria from AstraZeneca. QC; participated in advisory boards for AbbVie, Amgen, AnHeart, Astellas, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daichii Sankyo, Eli Lilly, Janssen, Jazz Pharmaceuticals, Merck, Novartis, Pfizer, Roche, and Takeda; has received research funding from AstraZeneca; and has participated on data and safety monitoring boards for Merck. CL; participated on advisory boards or had a speaker's agreement with AbbVie, Alethia Therapeutics Inc., Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Jazz Pharmaceuticals, Jounce Therapeutics, LEO Pharma, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Trizell Ltd, United Therapeutics and Xcovery. BS; participated on advisory boards for Bristol Myers Squibb, Novartis, Takeda, Janssen and Pfizer; and had a speaker's agreement with AstraZeneca. JK; employee and stockholder of Novartis. AFF; employee and stockholder of Novartis. MST; received research funding from AstraZeneca, Bayer, and Sanofi; and received honoraria from AstraZeneca, Amgen, Bayer, Sanofi, Regeneron, and Daichii-Sankyo. BK; participated on advisory boards for AstraZeneca, Merck, Roche, Bristol Myers Squibb, and Medtronic. RJ; participated on advisory boards for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, EMD Sorono, Fusion Pharmaceuticals, Jazz Pharmaceuticals, Janssen Pharmaceuticals, Lilly, Merck Sharpe and Dohme, Novartis, Pfizer, Roche, Sanofi, and Takeda; has received research funding from Alkermes, Amgen, Astellas, AstraZeneca, BeiGene, Bold Therapeutics, Bristol Myers Squibb, Fusion Pharmaceuticals, Janssen Pharmaceuticals, Macrogenics, Merck Sharpe and Dohme, and Novartis; acted as a consultant for Bristal Myers Squibb, Merck Sharpe & Dhome, and Pfizer; and received honoraria from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Jazz Pharmaceuticals, Merck Sharpe & Dohme, Novartis, Roche, and Takeda. PAB; received honoraria from Merck, Abbvie, Lilly, and Pfizer; participated on advisory boards for Boehringer Ingelheim, Mirati, AstraZeneca and RAPT Therapeutics; and participated on data and safety monitoring boards for Mirati.
(Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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