TIP-16. Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS (LUMOS2) study

Abstract BACKGROUND Patients with progressive IDH-mutant grade 2-3 glioma have limited therapeutic options. The LUMOS1 pilot study established feasibility of a precision oncology approach using molecular profiling, with LUMOS2 introducing therapeutic arms. METHODS LUMOS2 (ANZCTR: ACTRN12623000096651) is a phase 2 umbrella trial for patients with recurrent IDH-mutant grade 2 or 3 glioma, representing a collaboration between the Cooperative Trials Group for Neuro-Oncology (COGNO), the Canadian Cancer Trials Group (CCTG) and Omico, with University of Sydney as trial sponsor. Eligible adult participants undergo re-resection to obtain contemporaneous tumor tissue for comprehensive genomic profiling (CGP). A multidisciplinary international Molecular Tumor Advisory Panel (MTAP) with neuro-oncology expertise appraise each CGP and provide a synthesized, tailored recommendation. LUMOS2 currently has four active arms each with n=19 participants: paxalisib (PIK3CA-MTOR inhibitor) for participants with PIK3CA pathway alterations, or randomization to one of three target-agnostic options: AK104 (PD-1/CTLA-4 bispecific antibody), selinexor (selective inhibitor of nuclear export), or niraparib plus AK104 (PARP inhibitor plus AK104). RESULTS Australian followed by Canadian site activation commenced 31 August 2023 and 14 November 2024 respectively. As of 13 May 2025, 10 Australian and 4 Canadian sites are recruiting, with 60 participants screened. Of these, 35 have been allocated and registered for trial therapy, 2 are in screening in the screening phase and 6 are awaiting CGP results. Screen failures occurred in n=17 a) pre-surgery in 4 (clinician decision n=2, participant withdrawal n=2); b) post-surgery pre-MTAP review in 10 (disease progression n=4, absent pathologically active tumour n=3, clinical deterioration n=2 and high-grade transformation n=1; and c) post-MTAP review prior to treatment n=3 (clinical deterioration in n=2 and participant preference n=1). CONCLUSIONS Feasibility of molecular guided therapy in recurrent grade 2-3 glioma based on comprehensive genomic profiling is established with trial recruitment to date.

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Journal
Neuro-Oncology
Published
2025-11-01
DOI
https://doi.org/10.1093/neuonc/noaf201.1676
Primary Topic
Glioma Diagnosis and Treatment
Type
article
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article

TIP-16. Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS (LUMOS2) study

Sonia Yip, Adam Cooper, Warren Mason, Chris J. O’Callaghan et al.
Neuro-Oncology
Glioma Diagnosis and Treatment
article

TIP-16. Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS (LUMOS2) study

Sonia Yip, Adam Cooper, Warren Mason, Chris J. O’Callaghan, Hui Kong Gan, Benhur Amanuel, Brandon Lau, Rosemary Anne Harrup, Elizabeth Helen Barnes, Ganessan Kichenadasse, Hao‐Wen Sim, David Roberge, Rebecca Harrison, Lucas Adda, James Lynam, Marshall Pitz, James Richard Whittle, Roel G.W. Verhaak, Elizabeth Ahern, Anthony Dowling, Benjamin Y. Kong, Subotheni Thavaneswaran, Michael E. Buckland, Helen Wheeler, Cynthia Hawkins, Lloyd S. Ralston, Mandy L. Ballinger, Richard De Abreu Lourenço, Royall M. Calder, Bryan W. Day, David M. Thomas, Paula de Robles, Zarnie Lwin, Neyra Solano, Eng-Siew Koh, M. Maddula, John Simes, Sachie Pallimulla, Andrew Norrie
article en

Abstract

Abstract BACKGROUND Patients with progressive IDH-mutant grade 2-3 glioma have limited therapeutic options. The LUMOS1 pilot study established feasibility of a precision oncology approach using molecular profiling, with LUMOS2 introducing therapeutic arms. METHODS LUMOS2 (ANZCTR: ACTRN12623000096651) is a phase 2 umbrella trial for patients with recurrent IDH-mutant grade 2 or 3 glioma, representing a collaboration between the Cooperative Trials Group for Neuro-Oncology (COGNO), the Canadian Cancer Trials Group (CCTG) and Omico, with University of Sydney as trial sponsor. Eligible adult participants undergo re-resection to obtain contemporaneous tumor tissue for comprehensive genomic profiling (CGP). A multidisciplinary international Molecular Tumor Advisory Panel (MTAP) with neuro-oncology expertise appraise each CGP and provide a synthesized, tailored recommendation. LUMOS2 currently has four active arms each with n=19 participants: paxalisib (PIK3CA-MTOR inhibitor) for participants with PIK3CA pathway alterations, or randomization to one of three target-agnostic options: AK104 (PD-1/CTLA-4 bispecific antibody), selinexor (selective inhibitor of nuclear export), or niraparib plus AK104 (PARP inhibitor plus AK104). RESULTS Australian followed by Canadian site activation commenced 31 August 2023 and 14 November 2024 respectively. As of 13 May 2025, 10 Australian and 4 Canadian sites are recruiting, with 60 participants screened. Of these, 35 have been allocated and registered for trial therapy, 2 are in screening in the screening phase and 6 are awaiting CGP results. Screen failures occurred in n=17 a) pre-surgery in 4 (clinician decision n=2, participant withdrawal n=2); b) post-surgery pre-MTAP review in 10 (disease progression n=4, absent pathologically active tumour n=3, clinical deterioration n=2 and high-grade transformation n=1; and c) post-MTAP review prior to treatment n=3 (clinical deterioration in n=2 and participant preference n=1). CONCLUSIONS Feasibility of molecular guided therapy in recurrent grade 2-3 glioma based on comprehensive genomic profiling is established with trial recruitment to date.

Neuro-OncologyVol. 27(Supplement_5)
BC Cancer Agency (CA), The University of Sydney (AU), University of Tasmania (AU), University of British Columbia (CA), The University of Queensland (AU), The University of Melbourne (AU), University of Calgary (CA), Flinders University (AU), University of Toronto (CA), Queen's University (CA), QIMR Berghofer Medical Research Institute (AU), Royal Brisbane and Women's Hospital (AU), Royal Prince Alfred Hospital (AU), Royal North Shore Hospital (AU), Peter MacCallum Cancer Centre (AU), Liverpool Hospital (AU), Hospital for Sick Children (CA), Sir Charles Gairdner Hospital (AU), Princess Margaret Cancer Centre (CA), Royal Hobart Hospital (AU), UNSW Sydney (AU), Yale University (US), St Vincent's Hospital Melbourne (AU), CancerCare Manitoba (CA), Cooperative Trials Group for Neuro-Oncology (AU), The Centre for Health (New Zealand) (NZ), Prince of Wales Hospital (AU), Personalis (United States) (US), Monash Health (AU), Adelaide Institute for Sleep Health (AU), BC Cancer Foundation (CA), Calvary Mater Newcastle Hospital (AU), Olivia Newton-John Cancer Wellness & Research Centre (AU), Pathwest Laboratory Medicine (AU), Monash University (AU), Western Sydney University (AU), Université de Montréal (CA), University of Newcastle Australia (AU), Newcastle University (GB)
Openalex Percentile: Top 52%
Glioma Diagnosis and Treatment
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