Ctim-27. Pembrolizumab in Combination With the Multipeptide Vaccine Ima950 Adjuvanted With Poly-Iclc for Relapsing Glioblastoma: A Randomized Phase I/Ii Trial (Ima950-106)

Immunotherapy offers a promising alternative approach for patients with glioma. In this study, we conducted a phase I/II clinical trial to evaluate the safety and tolerability of a multipeptide therapeutic vaccine (IMA950) comprising nine GBM-associated HLA-A2-restricted and two tumor-associated MHC class II-restricted peptides administered in combination with the adjuvant Poly-ICLC with or without pembrolizumab in patients with relapsing GBM or grade IV astrocytoma. Patients received up to nine subcutaneous injections of IMA950/Poly-ICLC without (Arm 1) or with (Aim 2) pembrolizumab (200 mg IV every 3 weeks). Primary endpoints were safety and tolerability; secondary endpoints included overall survival (OS), progression-free survival (PFS) as well as analysis of vaccine-induced T cell responses in the peripheral blood and tumor and treatment-induced changes in the tumor microenvironment (TME). This clinical trial showed that the IMA950/Poly-ICLC vaccine administered with or without pembrolizumab was safe and well tolerated. No differences in OS and PFS were observed between the two arms. Vaccine-induced CD8 and CD4 T cell responses were detected in peripheral blood samples collected before, during and after vaccination in some individuals but were of low magnitude. Tumor samples collected before treatment and after the 4th vaccine were submitted to single-nuclei (n=11) and bulk (n=19) RNA sequencing for transcriptomic analysis. Expression of the vaccine antigen in tumors was heterogeneous across patients, and no significant loss of antigen expression was observed following treatment in either arm. Single-nuclei RNA sequencing revealed that tumor cells predominantly exhibited astrocyte-like, oligodendrocyte progenitor-like and neural progenitor-like states. Exploratory analysis of the TME revealed the presence of SPP1⁺ and M2-like macrophages. Additionally, a distinct cluster of CD8⁺ IL7Rhi T cells was identified in both pre- and post-treatment samples across both treatment arms. Altogether, the IMA950/Poly-ICLC vaccine administered with or without pembrolizumab is safe but did not significantly impact patient survival.