OS03.5.A A PHASE I CLINICAL TRIAL ON THE INTRACRANIAL ADMINISTRATION OF AUTOLOGOUS CD1C(BDCA-1)+ /CD141(BDCA-3)+ MYELOID DENDRITIC CELLS IN COMBINATION WITH IPILIMUMAB AND NIVOLUMAB IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMA

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2024-10, Vol.26 (Supplement_5), p.v17-v17
• Main Authors: Duerinck, J, Lescrauwaet, L, Dirven, I, Del’haye, J, Cammaert, M, Geens, W, Geeraerts, X, Stevens, L, Brock, S, Kockx, M, Everaert, H, Vanbinst, a, Tuyaerts, S, Neyns, B
• Format: Article
• Language: English
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noae144.048

Abstract BACKGROUND Intracranial (iCran) administration of the PD-1 and CTLA-4 blocking monoclonal antibodies nivolumab (NIVO) and ipilimumab (IPI) at the time of resection of recurrent high-grade glioma (rHGG) is safe and resulted in encouraging survival (NCT03233152). CD1c(BDCA-1)+ /CD141(BDCA-3)+ myeloid dendritic cells (myDC) play a pivotal role in initiating an adaptive anti-tumor immune response and licensing immune anti-tumor effector cells within the tumor microenvironment. iCran injection of autologous myDC in pts with rHGG was found to be safe but the potential added benefit for survival has not been established. MATERIAL AND METHODS rHGG pts (after prior RT and TMZ, not in need of supraphysiological doses of corticotherapy), underwent leukapheresis followed by isolation/cryopreservation of myDC. NIVO (10 mg IV) was administered preoperatively. Autologous myDC (5-, 10-, or 20.106 cells) were injected into the brain tissue lining the resection cavity (iCer) following a maximal safe resection (MSR) or intratumorally (iTum) following a stereotactic core needle biopsy (SCNB). IPI (5 mg) plus NIVO (10 mg) were co-injected iCer or iTum with the myDC. Postoperative NIVO was administrated intracavitary via an Ommaya reservoir (iCav, 10 mg) and intravenously (IV, 10 mg) Q2w (max 11x). RESULTS 21 pts (13 M; med 49 y [range 20 -78]; IDHwt 17 pts, ECOG PS 0 or 1: 18-, 3 pts) underwent procurement of myDC; intraoperative administration of myDC was preceded by MSR in 19 pts, and SCNB in 2 pts. Respectively 6-, 3-, and 12 pts were treated at the 3 myDC dose levels. All pts received the peri-op iTum/iCer/IV-administration of IPI and NIVO as planned. The median postoperative iCav and IV NIVO-administration was 7 (range 0-11) and 8 (0-11). Study treatment was discontinued early at first progression in 9- and AE in 3 pts. Most important TRAEs: bacterial colonization of the Ommaya reservoir (n=4), craniotomy wound dehiscence (n=2), and bacterial meningitis (n=1). At DBL (01MAY2024), 6 pts (29%) remain progression-free (incl. 3 pts with >2y PFS). PFS (med. 24w [95% CI 8- 39]) is superior when compared to the pts (n=70) with resectable rHGG treated in 4 other cohorts of the GlITIpNi trial (p=.003). When including a durable benefit from bevacizumab at first PD in 3 pts (out of 10 pts who were treated with a low-dose bevacizumab regimen at first progression), PFS compared favorably to a historical pooled cohort (n: 469) of rHGG treated with VEGF(R)-inhibitors (p=.007).