CTIM-36 - Immunohistochemistry evaluation on pre-treatment tumor tissue predicts treatment response to MN-166 (ibudilast) and Temozolomide combination therapy in glioblastoma patients.

Friday, November 17, 2023

7:30 PM – 9:30 PM PT

Location: Exhibit Hall A/B

Poster Presenter(s)

Justin D. Lathia

Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute
Cleveland, Ohio, United States

Author(s)

Adam J. Lauko

Cleveland Clinic
Cleveland, Ohio, United States
Km

Kazuko matsuda

MediciNova Inc
La Jolla, United States
MM

Malath Makhay

MediciNova Inc.
La Jolla, United States
Lakshmi Nayak

Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Ugonma N. Chukwueke

Dana-Farber Cancer Institute
BOSTON, Massachusetts, United States
Eudocia Q. Lee

Dana-Farber Cancer Institute, Boston, MA
Boston, Massachusetts, United States
David A. Reardon

Center for Neuro-Oncology, Dana-Farber Cancer Institute
Boston, Massachusetts, United States
RB

Rameen Beroukhim

Center for Neuro-Oncology, Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Tracy T. Batchelor

Brigham and Women’s Hospital Harvard Medical School
Boston, Massachusetts, United States
Elisa Aquilanti

Dana Farber Cancer Institute
Boston, Massachusetts, United States
Patrick Y. Wen

Dana-Farber Cancer Institute
Boston, Massachusetts, United States

STUDY

Design: MN-166-GBM-1201 is a Phase I/II open-label clinical trial to evaluate MN166 (ibudilast) and temozolomide (TMZ) combination treatment in newly diagnosed and recurrent glioblastoma (GBM) patients. 62 GBM patients (34 newly diagnosed and 28 recurrent) were enrolled in the study. All patients received MN-166 and TMZ combination treatment until disease progression or withdrawal from the study for other reasons.

Methods: Pre-treatment tumor tissue at initial surgery from 24 study participants was evaluated to determine potential predictors of response to MN-166, which has been shown to inhibit the interaction between macrophage migration inhibitory factor (MIF) and CD74 with ERK phosphorylation downstream of CD74. We looked at CD11b and CD3 expression to characterize the immune profile within the tumors and Ki67 to determine percentage of proliferating tumor cells, all of which were calculated by a masked researcher. Then, patients were stratified based on progression within the first five months after receiving MN-166 and TMZ.

Results: Patients who did not progress within 5 months had a significantly lower percentage of CD3+ T cell infiltration than nonresponding patients (p=0.045), and CD74 expression was lower in patients with no progression (p=0.16). The other markers demonstrated no differences. MN-166 and TMZ combination therapy was generally safe and well tolerated.

Conclusion: CD3 expression was a good predictor for tumor progression for five months in recurrent GBM patients treated with MN-166 and TMZ. T cell infiltration within GBM tumors has been an active area of research with the success of immune checkpoint blockade (ICB) therapies in other cancers. Moreover, MN-166 has been shown to impact immune suppressive myeloid cells, which are linked to the immune suppressive tumor microenvironment and a resistance mechanism to ICB. Collectively, we postulate that the efficacy of MN-166 for treatment of GBM could be further enhanced by co-treatment with ICBs.