Sotorasib (960 mg or 240 mg) once daily in patients with previously treated KRAS G12C-mutated advanced NSCLC.

Diarrhea Dose comparison Gastrointestinal toxicity Pharmacokinetics

Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
05 Jul 2024
Historique:
received: 10 05 2024
revised: 20 06 2024
accepted: 28 06 2024
medline: 20 7 2024
pubmed: 20 7 2024
entrez: 19 7 2024
Statut: aheadofprint

Résumé

Sotorasib 960 mg once daily is approved to treat KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Sotorasib exhibits non-dose proportional pharmacokinetics and clinical responses at lower doses; therefore, we evaluated the efficacy and safety of sotorasib 960 mg and 240 mg. In this phase 2, randomized, open-label study, adults with KRAS G12C-mutated advanced NSCLC received sotorasib 960 mg or 240 mg once daily. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and pharmacokinetics. The study was not powered for formal statistical hypothesis testing. In the 960 mg group (n = 104), ORR was 32.7 % and DCR was 86.5 %. In the 240 mg group (n = 105), ORR was 24.8 % and DCR was 81.9 %. Median PFS was 5.4 months (960 mg) and 5.6 months (240 mg). At a median follow-up of 17.5 months, median OS was 13.0 months (960 mg) and 11.7 months (240 mg). AUC Patients treated with sotorasib 960 mg once daily had numerically higher ORR and DCR, and longer DOR and OS, than patients treated with 240 mg in this descriptive analysis. TEAEs were manageable with label-directed dose modifications. NCT03600883.

Sections du résumé

BACKGROUND BACKGROUND
Sotorasib 960 mg once daily is approved to treat KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Sotorasib exhibits non-dose proportional pharmacokinetics and clinical responses at lower doses; therefore, we evaluated the efficacy and safety of sotorasib 960 mg and 240 mg.
METHODS METHODS
In this phase 2, randomized, open-label study, adults with KRAS G12C-mutated advanced NSCLC received sotorasib 960 mg or 240 mg once daily. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and pharmacokinetics. The study was not powered for formal statistical hypothesis testing.
RESULTS RESULTS
In the 960 mg group (n = 104), ORR was 32.7 % and DCR was 86.5 %. In the 240 mg group (n = 105), ORR was 24.8 % and DCR was 81.9 %. Median PFS was 5.4 months (960 mg) and 5.6 months (240 mg). At a median follow-up of 17.5 months, median OS was 13.0 months (960 mg) and 11.7 months (240 mg). AUC
CONCLUSIONS CONCLUSIONS
Patients treated with sotorasib 960 mg once daily had numerically higher ORR and DCR, and longer DOR and OS, than patients treated with 240 mg in this descriptive analysis. TEAEs were manageable with label-directed dose modifications.
CLINICAL TRIAL REGISTRATION BACKGROUND
NCT03600883.

Identifiants

DOI: 10.1016/j.ejca.2024.114204 PMID: 39029295
pubmed: 39029295
pii: S0959-8049(24)00860-8
doi: 10.1016/j.ejca.2024.114204
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT03600883']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

114204

Informations de copyright

Copyright © 2024. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. J. Hochmair: Financial Interests, Personal, Other, Consulting or Advisory role: Takeda, Roche, Lilly, AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Lilly, MSD Oncology, Novartis, Roche, Amgen. K. Vermaelen: Financial Interests, Personal, Research Grant: Bristol Myers Squibb (BMS); Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Support for Attending Meetings: AstraZeneca, BMS, Merck; Financial Interests, Personal, Other, Patents Planned/Issued/Pending: Ghent University; Financial Interests, Personal, Other, Data Safety Monitoring Board or Advisory Board: Amgen, AstraZeneca, BMS, Merck. G. Mountzios: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, BMS GmbH & Co. KG, Boehringer Ingelheim, MSD, Novartis, Roche, Takeda; Financial Interests, Personal, Other, Consulting or Advisory Board: Amgen, AstraZeneca/Greece, BMS GmbH & Co. KG, MSD, Novartis, Roche, Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, BMS GmbH & Co. KG, Ipsen, MSD, Novartis, Roche. E. Carcereny: No conflicts to disclose. C. Dooms: No conflicts to disclose. S.-H. Lee: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca/MedImmune, Lilly, Merck, Roche; Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca, BMS/Ono, IMBdx, Janssen, Lilly, Merck, Pfizer, Roche, Takeda; Financial Interests, Personal, Research Grant: AstraZeneca, Lunit, Merck; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis. E. Morocz: No conflicts to disclose. T. Kato: Financial Interests, Personal, Advisory Board, Speaker, Consultancy: AstraZeneca, Eli Lilly, Merck Biopharma, MSD; Financial Interests, Personal, Advisory Board, Speaker: Pfizer, Amgen, Janssen; Financial Interests, Personal, Other, Consultancy: Daiichi Sankyo, Takeda, Taiho; Financial Interests, Personal, Other, Consultancy, Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Ono, Novartis, BMS, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: BeiGene, GSK; Financial Interests, Personal, Advisory Board, Steering Committee: Roche; Financial Interests, Personal, Full or Part-Time Employment, Family Member: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Chugai, MSD, Pfizer, Eli Lilly, AbbVie, Regeneron, Novartis, Amgen, Merck Biopharma, Haihe Biopharma, Blueprint Medicines, Turning Point, BeiGene, Gilead, GSK, Janssen, Bayer, Takeda, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Local PI: AstraZeneca. T.-E. Ciuleanu: Financial Interests, Personal, Other, Consulting or Advisory Role: Astellas Pharma, Janssen, BMS, Merck Serono, Amgen, Roche, Pfizer, Boehringer Ingelheim, Eli Lilly, AstraZeneca, Merck Sharp & Dohme (MSD), Sanofi, Novartis, Servier, A&D Pharma; Financial Interests, Personal, Other, Travel Support: Pfizer, Sanofi, Boehringer Ingelheim, Merck, Servier, Ipsen, Amgen, A&D Pharma, AstraZeneca, Genentech, BMS, MSD Oncology, Eli Lilly, Janssen, Novartis, Astellas Pharma. G. K. Dy: Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca, Mirati Therapeutics, Lilly, Amgen, Regeneron, Eli Lilly; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Mirati Therapeutics, Lilly, Sanofi, BioAtla, Regeneron, Iovance Biotherapeutics, Revolution Medicines. B. Parente: No conflicts to disclose. K. J. O’Byrne: Financial Interests, Personal, Stocks/Shares: Carpe Vitae Pharmaceuticals, DGC Diagnostics, Replica Pharmaceuticals; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Ipsen, Janssen-Cilag, Merck Group, MSD, Novartis, Pfizer, Roche, Seagen, Takeda, TriStar, Yuhan; Financial Interests, Personal, Other, Consulting or advisory Role: Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Ipsen, Janssen-Cilag, MSD, Novartis, Pfizer, Roche/Genentech, Sanofi, Seagen, Yuhan; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: three active patents. Q. S. Chu: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AnHeart Therapeutics, Astellas, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Jazz Pharmaceutical, Johnson and Johnson, Merck, Novartis, Pfizer, Roche, Takeda. G. De Castro Jr.: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Pfizer, MSD, BMS, Novartis, Roche, Amgen, Janssen, Merck Serono, Daiichi Sankyo, Sanofi, Lilly; Financial Interests, Personal, Other, Consulting or Advisory Role: Boehringer Ingelheim, Pfizer, Bayer, Roche, MSD, BMS, AstraZeneca, Yuhan, Merck Serono, Janssen, Libbs, Sanofi, Novartis, Daiichi Sankyo, Lilly; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bayer, Novartis, Roche, Merck Serono, BMS, MSD, Boehringer Ingelheim, Pfizer, Janssen, Amgen, Lilly, Daiichi Sankyo; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD, Novartis, Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bayer, BMS, Merck Serono, Daiichi Sankyo. N. Girard: Financial Interests, Personal, Research Grant: AstraZeneca, Amgen, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Novartis, Pfizer, Sivan, Trizell; Financial Interests, Personal, Other, Consulting or Advisory Role: BMS, AstraZeneca, AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Mirati, Novartis, Pfizer, Roche, Sanofi, Sivan; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Invited Speaker, Participation in Data Safety Monitoring Board: Roche; Financial Interests, Personal, Other, Leadership Role: International Thymic Malignancy Interest Group; Financial Interests, Personal, Full or Part-Time Employment, Employment of a Family Member: AstraZeneca. W. Snyder, Q. Tran, W. Kormany, B. Houk, B. Mehta: Financial Interests, Personal, Full or Part-Time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. A. Curioni-Fontecedro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis, Amgen, Roche, Takeda, Janssen; Non-Financial Interests, Personal, Leadership Role: Swiss Academy for Clinical Cancer Research (SAKK); Non-Financial Interests, Personal, Principal Investigator of Clinical Trials: Roche; Non-Financial Interests, Personal, Principal Investigator, Clinical Trials: Takeda, MSD, BMS.

Auteurs

Maximilian J Hochmair (MJ)

Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria. Electronic address: maximilian.hochmair@gesundheitsverbund.at.

Karim Vermaelen (K)

Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Oost-Vlaanderen, Belgium.

Giannis Mountzios (G)

Department of Medical Oncology and Clinical Trials Unit, Henry Dunant Hospital Center, Athens, Greece.

Enric Carcereny (E)

Medical Oncology Department, Catalan Institute of Oncology Badalona, Badalona Applied Research Group in Oncology, Badalona, Barcelona, Spain.

Christophe Dooms (C)

Department of Respiratory Diseases, University Hospitals KU Leuven, Leuven, Belgium.

Se-Hoon Lee (SH)

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Eva Morocz (E)

Pulmonology Hospital, Törökbálint, Hungary.

Terufumi Kato (T)

Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan.

Tudor-Eliade Ciuleanu (TE)

Institutul Oncologic Prof Dr Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.

Grace K Dy (GK)

Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Barbara Parente (B)

Pulmonology Department, Hospital CUF Porto, Porto, Portugal.

Kenneth J O'Byrne (KJ)

Princess Alexandra Hospital, Translational Research Institute and Queensland University of Technology, Brisbane, Queensland, Australia.

Quincy S Chu (QS)

Division of Medical Oncology, Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.

Gilberto De Castro Junior (G)

Hospital Sírio Libanês, São Paulo, Brazil.

Nicolas Girard (N)

Institut du Thorax Curie Montsouris, Institut Curie, Paris, France; UVSQ, Paris Saclay, Versailles, France.

Wendy Snyder (W)

Amgen Inc., Thousand Oaks, CA, USA.

Qui Tran (Q)

Amgen Inc., Thousand Oaks, CA, USA.

William Kormany (W)

Amgen Inc., Thousand Oaks, CA, USA.

Brett Houk (B)

Amgen Inc., Thousand Oaks, CA, USA.

Bhakti Mehta (B)

Amgen Inc., Thousand Oaks, CA, USA.

Alessandra Curioni-Fontecedro (A)

Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland; University of Fribourg and Hospital of Fribourg, Fribourg, Switzerland.

Classifications MeSH