IMA950 / Immatics, Cancer Research UK, University Hospitals of Geneva - LARVOL DELTA

Immunotherapeutic Advances in Glioma Management: The Rise of Vaccine-Based Approaches (EANO 2024) - "For example, the IMA950 peptide vaccine resulted in progression-free survival rates of 74% at 6 months and 31% at 9 months in newly diagnosed GBM patients. Similarly, the SurVaxM peptide vaccine led to 95.2% of patients remaining progression-free at 6 months, with an average progression-free survival of 11.4 months and an overall survival of 25.9 months...Dendritic cell vaccines, such as DCVax-L and α-type-1 DC vaccines, demonstrated improvements in overall survival in GBM patients, with long-term benefits observed in patients with a methylated MGMT promoter... Glioma vaccines show promise in stimulating immune responses against tumours, offering potential benefits alongside standard treatments. Challenges in assessing vaccine efficacy and addressing treatment-related adverse effects emphasise the need for further research and clinical trials. Challenges like tumour heterogeneity and immune evasion persist, but advances in genetic engineering and immunotherapy offer hope..."

IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • CSF2

A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov) - P1 | N=14 | Terminated | Sponsor: Nicholas Butowski | Active, not recruiting ➔ Terminated; Industry sponsor decision

Trial termination • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioma • Oligodendroglioma • Oncology • Solid Tumor • CD4 • CD8

The role of TNC in atherosclerosis and drug development opportunities. (PubMed, Int J Biol Sci) - "The F16-conjugate agent F16IL2 is undergoing clinical trials...Furthermore, ATN-RNA and IMA950 were investigated in clinical trials as therapeutic drugs and vaccines by targeting TNC, respectively. Therefore, targeting TNC could greatly improve the success rate of atherosclerosis-targeted drugs and/or specific drug development. This review discussed the role of TNC in atherosclerosis, atherosclerosis-targeted drug delivery vectors, and agent development to provide knowledge for drug development targeting TNC."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia

A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas. (PubMed, Neuro Oncol) - "The combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients."

Journal • Brain Cancer • CNS Tumor • Glioma • Hematological Malignancies • Oncology • Solid Tumor • CD27 • CD4 • CD8

A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: Nicholas Butowski | Trial completion date: Dec 2022 ➔ Dec 2030

Trial completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioma • Oligodendroglioma • Oncology • Solid Tumor • CD4 • CD8

A multispecific non-integrating RNA CAR T platform to overcome the clinical challenge of glioblastoma heterogeneity. (ESMO-IO 2021) - P1/2 | "Methods Targets were selected from antigens identified by our group and currently being tested in a clinical trial as a multipeptide vaccine (IMA950/Poly-ICLC + pembrolizumab, NCT03665545), from previously reported CAR T cells as well as from relevant GBM antigens described in literature. Legal entity responsible for the study The authors. Funding ISREC Foundation."

Clinical • Heterogeneity • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

IMA950 multipeptide vaccine adjuvanted with poly-ICLC in combination with standard therapy in newly diagnosed HLA-A2 glioblastoma patients (ESMO-IO 2017) - P1/2; "Patients received the standard of care treatment including surgery, 6-week chemo-radiation therapy, and 6-12 adjuvant cycles of temozolomide. Conclusions Overall, the IMA950/Poly-ICLC vaccine is safe, immunogenic and preliminary median OS is encouraging. Definitive clinical results and correlation with immunological data will indicate the most efficacious route of vaccination for use in further trials in glioma patients."

Clinical • Combination therapy • Solid Tumor

IMA950-106: Pembrolizumab in Association With the IMA950/Poly-ICLC for Relapsing Glioblastoma (clinicaltrials.gov) - P1/2 | N=18 | Active, not recruiting | Sponsor: University Hospital, Geneva | Recruiting ➔ Active, not recruiting | Trial primary completion date: Oct 2021 ➔ Dec 2023

Enrollment closed • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • PD-L1

[VIRTUAL] Combination of the IMA950/Poly-ICLC Multipeptide Vaccine with Pembrolizumab in Relapsing Glioblastoma Patients (SNO 2020) - P1/2 | "Preliminary results show CD4 and CD8 T cell responses to the vaccine are detected in both groups in the peripheral blood. Analysis at the tumor site and comparison between arms will be performed once all patients have been included."

Clinical • IO biomarker • Glioblastoma • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • CD8

A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov) - P1; N=14; Active, not recruiting; Sponsor: Nicholas Butowski; Recruiting ➔ Active, not recruiting; N=30 ➔ 14

Clinical • Enrollment change • Enrollment closed • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioma • Immunology • Oligodendroglioma • Oncology • Solid Tumor • CD4 • CD8

A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Nicholas Butowski; Trial completion date: Jun 2021 ➔ Dec 2022; Trial primary completion date: Jun 2021 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioma • Immunology • Oligodendroglioma • Oncology • Solid Tumor • CD4 • CD8

Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. (PubMed, Neuro Oncol) - P1/2 | "We provide, in a clinical trial, using cell surface-presented antigens, insights into optimization of vaccines generating effector T cells for glioma patients. Clinicaltrials.gov NCT01920191."

Clinical • Journal • P1/2 data • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: University of California, San Francisco; Not yet recruiting ➔ Recruiting; Initiation date: Oct 2016 ➔ Jan 2017; Trial primary completion date: Oct 2017 ➔ Jan 2018

Enrollment open • Trial initiation date • Trial primary completion date • Biosimilar • Immunology • Oncology

A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multi Peptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma. (PubMed) - Clin Cancer Res - "IMA950 plus GM-CSF was well tolerated with the primary immunogenicity endpoint of observing multi-TUMAP responses in at least 30% of patients exceeded. Further development of IMA950 is encouraged."

Journal • Biosimilar • Oncology

A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Nicholas Butowski; Trial completion date: Sep 2020 ➔ Jun 2021; Trial primary completion date: Mar 2020 ➔ Jun 2021

Clinical • Trial completion date • Trial primary completion date

Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma (clinicaltrials.gov) - P1; N=25; Active, not recruiting; Sponsor: immatics Biotechnologies GmbH; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • IO Biomarker

Vaccine Therapy, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme (clinicaltrials.gov) - P1; N=45; Active, not recruiting; Sponsor: Cancer Research UK; Trial primary completion date: Dec 2013 ➔ Feb 2015

Clinical • Trial primary completion date

Vaccine Therapy, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme (clinicaltrials.gov) - P1; N=45; Completed; Sponsor: Cancer Research UK; Active, not recruiting ➔ Completed

Clinical • Trial completion

Vaccine Therapy, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme (clinicaltrials.gov) - P1; N=45; Active, not recruiting; Sponsor: Cancer Research UK; Completed ➔ Active, not recruiting

Clinical • Enrollment closed

Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma (clinicaltrials.gov) - P1; N=6; Terminated; Sponsor: immatics Biotechnologies GmbH; This decision was taken without any safety reasons. Since beginning of the study (June 2011) only six patients were enrolled.

Clinical • IO Biomarker • Trial termination

Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma (clinicaltrials.gov) - P1; N=6; Terminated; Sponsor: immatics Biotechnologies GmbH; N=25 ➔ 6

Clinical • Enrollment change • IO Biomarker

Vaccine-based immunotherapeutic approaches to gliomas and beyond. (PubMed, Nat Rev Neurol) - "Other approaches in early phases of clinical development employ multipeptide vaccines such as IMA-950, cytomegalovirus-derived peptides, or tumour-derived peptides such as heat shock protein-96 peptide complexes and the Arg132His mutant form of isocitrate dehydrogenase. However, some preclinical trial data suggest that addition of immunomodulatory reagents such as immune checkpoint inhibitors, transforming growth factor-β inhibitors, signal transducer and activator of transcription 3 inhibitors, or modifiers of tryptophan metabolism could augment the therapeutic activity of vaccination and overcome glioma-associated immunosuppression."

IO Biomarker • Journal • Review