The optimal adjuvant alkylating chemotherapy regimen for high-risk WHO grade 2 glioma in the molecular era remains uncertain. We evaluated real-world treatment patterns, toxicity, and outcomes following radiotherapy with adjuvant temozolomide (TMZ) or procarbazine, lomustine, and vincristine (PCV) in a multicentre Canadian cohort. PROTECT is a retrospective multicentre cohort study including adults with clinically defined high-risk WHO grade 2 diffuse glioma treated with radiotherapy and adjuvant alkylating chemotherapy. Clinical, molecular, treatment delivery, toxicity, surveillance, and survival data were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test and Cox regression. A total of 116 patients were included, with a median follow-up of 71 months. Isocitrate dehydrogenase (IDH) mutation was present in 84.6

Background The majority of patients diagnosed with glioblastoma are >60 years. Three randomized trials addressed the roles of radiotherapy (RT) and temozolomide (TMZ) for elderly patients. NORDIC and NOA-08 compared RT versus TMZ, while CE.6 randomized between hypofractionated RT and RT + TMZ. All showed significant benefits for the TMZ arms, especially for those patients with O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumors. This pooled analysis aimed at identifying additional factors that could improve individualized treatment recommendations. Methods Analyses were performed separately in the RT and TMZ arms of the pooled NORDIC and NOA-08 data, and in the RT and TMZ/RT arms of CE.6. The prognostic value of baseline clinical factors, comorbidities, and quality of life (QoL) scores were assessed. Results NORDIC + NOA-08 (NN) included 715 patients and CE.6 included 562 patients. Median age for NN was 71 and 73 years for CE.6. In NN and CE.6 respectively, 66.2% versus 70.5% underwent resection and 50.9% and 75.3% were on steroids. In NN, 401 patients received RT alone and 281 in CE.6, while 314 were randomized to TMZ alone in NN and 281 to concomitant RT + TMZ in CE.6. Known clinical prognostic factors, such as extent of resection and WHO performance status were confirmed, as was MGMT promoter methylation status for TMZ-treated patients. TMZ-treated patients with 2 or 3 comorbidities; hypertension, diabetes, and/or stroke had worse survival, both in NN (P = .022) and CE.6 (P = .022). Baseline QoL had a minor association with outcome. Conclusion Consideration of comorbidities allows improved personalized treatment decisions for elderly glioblastoma patients.

Recurrent or refractory IDH-mutant (mt) gliomas represent a population with significant unmet clinical need. The Notch ligand delta-like 3 (DLL3) is a tumor-associated antigen that is highly and homogeneously expressed in IDH-mt gliomas but absent in normal brain tissue, making it an attractive therapeutic target. Tarlatamab is a half-life extended bispecific T-cell engager that targets DLL3 and CD3 to redirect cytotoxic T cells toward DLL3-expressing tumor cells. Given the specific expression of DLL3 in IDH-mt gliomas and promising activity of tarlatamab in other DLL3-positive tumors, this study investigates the safety, efficacy, and intracranial activity of tarlatamab in this patient population. TARGID is an open-label, phase II trial enrolling adult patients with histologically confirmed IDH1 or IDH2-mt astrocytoma or oligodendroglioma following up to two prior lines of systemic therapies. The study comprises two cohorts. Cohort 1 (n=10) includes patients with resectable disease who will receive up to three cycles of tarlatamab prior to surgery; postoperative continuation is permitted. The primary endpoint for this cohort is the change in CD8+ T-cell infiltration in tumor tissue and blood. Cohort 2 (n=34) includes patients with unresectable disease and uses a Simon’s optimal two-stage design (H0: P ≤ 0.1 versus H1: P ≥ 0.25). In the 1st stage, 13 patients will be accrued. If 2 or more responses are observed, 21 additional patients will be enrolled. Tarlatamab is administered intravenously at 10 mg every two weeks, following a 1 mg priming dose on Cycle 1 Day 1. The primary endpoint is objective response rate by RANO 2.0. Exploratory endpoints include DLL3 expression, circulating biomarkers, and immune correlatives. The trial is currently in activation, with first patient enrollment anticipated in Q3 2025. The study is supported by the provision of study drug from Amgen as an investigator-initiated trial.

Recurrent IDH-mutant gliomas pose a significant therapeutic challenge, with limited treatment options following progression after standard therapy. Combining PARP inhibitors with immune checkpoint blockade has been proposed as a synergistic strategy in IDH-mutant high-grade gliomas, leveraging vulnerabilities in homologous recombination repair and increased PD-L1 expression following PARP inhibition. This phase II trial (NCT03991832) evaluated the combination of the PARP inhibitor olaparib and the PD-L1 inhibitor durvalumab in patients with recurrent IDH-mutant glioma. We also investigated the potential of the plasma tumor methylome as a non-invasive biomarker of treatment response. Twenty-nine patients (median age 40.5 years; 41% female) were enrolled between January 2020 and February 2023. All patients received olaparib (300 mg twice daily) and durvalumab (1,500 mg IV every four weeks) until radiographic or clinical progression. Plasma samples were collected at baseline and monthly, and cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) was performed. The objective response rate was 10%, and median overall survival was 9.3 months. Longitudinal cfMeDIP-seq profiling enabled development of a circulating methylome classifier that accurately distinguished responders from non-responders. Integration with matched tumor transcriptomic and methylation data revealed enrichment of immune and DNA repair pathways in responders. Whole-exome sequencing identified no consistent mutational correlates. Spatial transcriptomic analysis demonstrated a more interactive, immune-rich tumor microenvironment and reduced malignant cell state diversity in responders. This study supports the safety of combined PARP and PD-L1 blockade in recurrent IDH-mutant glioma and highlights the plasma methylome as a promising non-invasive biomarker of therapeutic response.

PURPOSE STELLAR (ClinicalTrials.gov identifier: NCT02796261 ) was a phase III, randomized, open-label trial of eflornithine + lomustine versus lomustine monotherapy in patients with recurrent grade 3 astrocytoma. METHODS At trial initiation, eligibility criteria included: age ≥18 years, anaplastic astrocytoma (2016 WHO CNS Tumor classification [WHO CNS4]), first recurrence ≥6 months after radiation and temozolomide (TMZ), Karnofsky performance status ≥70, and no imaging findings consistent with grade 4 glioblastoma. Random assignment (1:1) was stratified by isocitrate dehydrogenase ( IDH ) mutation, age, resection extent, and geography. Patients received eflornithine (2.8 g/m 2 orally, every 8 hours [2 weeks on, 1 week off]) + lomustine (90 mg/m 2 orally, once every 6 weeks), or lomustine monotherapy (110 mg/m 2 once every 6 weeks). The primary end point was overall survival (OS). RESULTS Among 343 patients randomly assigned across 74 sites in eight countries, there was no difference in survival between eflornithine + lomustine and lomustine monotherapy (median OS 23.4 v 20.3 months, hazard ratio [HR], 0.94). Following changes in classification and grading in the 2021 WHO CNS5, a subset analysis of patients with IDH- mutant, grade 3 astrocytoma (n = 196), defined in 2024, before unblinding, showed clinically meaningful improvements in median OS with eflornithine + lomustine versus lomustine monotherapy (34.9 v 23.5 months, HR, 0.64) and median progression-free survival (PFS, 15.8 v 7.2 months, HR, 0.57). No differences were observed among patients with CNS grade 4 disease. Grade ≥3 treatment-emergent adverse events of relevance were related to reversible myelosuppression (eflornithine + lomustine 42% v lomustine monotherapy 29% of patients) and hearing impairment (24% v 0%). No new safety signals were identified. CONCLUSION Clinically meaningful improvements were observed; eflornithine + lomustine doubled PFS and improved OS in patients with recurrent IDH -mutant, grade 3 astrocytoma, but not grade 4 tumors, after prior radiotherapy and TMZ, consistent with its cytostatic mechanism of action.

The G8 screening assessment tool has been validated to assess frailty risk in older patients with cancer. A score of 14 or less is considered to identify patients at risk of frailty. The G8 has been implemented for all EORTC clinical trials including patients 70 years or older since 2017. Here we assessed the prognostic value of the G8 at baseline in older patients with newly diagnosed glioblastoma enrolled in clinical trials. Data from 83 patients aged 70 or older enrolled in the 1608 STEAM trial (NCT 03224104) (n=20) or the 1709 MIRAGE trial (NCT 03345095) (n=63) were analyzed. We defined a G8 low (≤14) and a G8 high group (15-17). The median age was 73 years, 29 patients (34.9 %) were female, 54 patients (65.1 %) were male. The KPS was 90 or more in 42 patients (50.6 %). Steroids were taken at baseline by 33 patients (39.8 %). 38 patients (45.8 %) were assigned to the G8 low group, and 45 patients (54.2 %) to the G8 high group. Patients with a KPS of 90 or 100 were more often in the G8 high group (adjusted OR = 6.98, 95% CI 2.19 – 25.64). Patients in the G8 high group had higher means for global health status scale and functioning scores at baseline than patients in the G8 low group. Treatment delivery measured by the relative dose intensity was better in patients with a high G8 than in patients with a low G8 (OR = 2.26, 95% CI 0.81- 6.53). Patients in the G8 low group tended to experience more toxicity than patients in the G8 high group. Patients in the G8 high group had a longer progression-free (adjusted HR = 0.37, 95% CI 0.20 – 0.68, p=0.0013) and overall survival (adjusted HR = 0.40, 95% CI 0.21 – 0.75, p=0.0045). The G8 score may be a powerful tool for prognostic assessment and for patient stratification in old patients with glioblastoma.

PURPOSE:The multicentre randomised phase III trial EORTC-1709-BTG/CCTG CE.8 (MIRAGE) (NCT03345095) analysed the addition of the proteasome inhibitor marizomib to temozolomide-based chemoradiotherapy with 60 Gy in 30 fractions in patients with newly diagnosed glioblastoma. Here, we analysed the benchmark case procedure for delineation and planning radiotherapy quality assurance (RTQA) that was performed before patient inclusion. MATERIALS AND METHODS:Prior to trial activation, all participating centers were required to submit a benchmark case for radiotherapy volume delineation and planning. Submissions were prospectively reviewed by the RTQA team, and in cases of unacceptable variations, centers were required to revise and resubmit the same case until protocol compliance was achieved. Structure sets and dose distributions of the same benchmark patient submitted by participating centres were analysed. We determined the rate and causes of variations of glioblastoma target volumes (TV) and organs at risk (OAR) from the protocol-specified delineation guidelines. Delineation interobserver variability before and after RTQA review were quantified using the Dice similarity coefficient (DSC) with respect to ground truth contours at first and final submission of the benchmark case. The influence of reducing delineation interobserver variability on dose parameters of ground truth structures was determined. RESULTS:The delineations by 88 institutes were judged by RTQA reviewers to contain "unacceptable" variations in 80 % (n = 70) of the cases. TV contours were more frequently deemed unacceptable than organs at risk (72 % vs 55 %). After RTQA review, the mean DSC significantly improved for TV (GTV: 0.77 vs 0.82, p = 0.002; CTV: 0.85 vs 0.88, p < 0.0001; PTV: 0.85 vs 0.88, p < 0.0001), brainstem (0.87 vs 0.88, p = 0.007), cochlea (0.58 vs 0.62, p = 0.004) and optic nerve (0.65 vs 0.67, p = 0.0005), indicating reduced interobserver variability. The delineation adjustments after RTQA review resulted in a significant increase of the mean CTV D98% (+2.2 Gy, +4%, p = 0.005), indicating an improved target coverage. Doses to organs at risk did not change significantly but still met predefined constraints. CONCLUSIONS:Variations in the delineation of target volumes and organs at risk were frequently judged as "unacceptable" during the RTQA review process. Besides a significant increase of CTV coverage, the impact of variations on organ at risk dosimetry was minor, suggesting a potentially negligible effect on toxicity outcomes. Quantitative metrics to assess delineation variations should be explored to improve the RTQA process in clinical trials and routine practice, aiming to flag delineation variations that confer an effect on tumour control or toxicity.

Patients with grade 2 IDH1/2 mutant (mIDH1/2) gliomas may experience symptoms (e. g. seizures) that impact their daily lives. Vorasidenib, an oral, brain-penetrant, dual inhibitor of mIDH1/2, has shown significant clinical benefits, including gradual tumor shrinkage, and a manageable safety profile in the Phase 3 INDIGO study. Herein, we investigate the potential relationship between vorasidenib and seizure rate, and between tumor volume and seizure activity in patients with mIDH1/2 glioma. Patients aged >12 years with grade 2 mIDH1/2 oligodendroglioma or astrocytoma, no prior treatment for glioma other than surgery, and no uncontrolled seizures were randomized 1:1 to receive vorasidenib 40 mg or placebo daily. Exploratory analyses for the number of on-treatment seizures were conducted in patients with more than 1 seizure in the baseline or on-treatment periods using a negative binomial regression model. The potential association between seizure activity and tumor volume was assessed using the mixed-effect model with repeated measurements. P-values were not prespecified. This analysis included 168 patients treated with vorasidenib (oligodendroglioma: n = 88; astrocytoma: n = 80) and 163 patients treated with placebo (oligodendroglioma: n = 84; astrocytoma: n = 79). Patients treated with vorasidenib had lower on-treatment rates of seizures than those treated with placebo (model-estimated rate of on-treatment seizures per person-year: 18.2 [95% confidence interval (CI) 8.4, 39.5] vs 51.2 [95% CI 22.9, 114.8]; ratio of rates: 0. 36 [95% CI 0.14, 0. 89]; P = 0.0263). There was a highly positive correlation between tumor volume and seizure number (log tumor size estimate of coefficient: 0.7; standard error: 0.26; P = 0.007). Treatment with vorasidenib was associated with lower seizure activity than with placebo in patients with mIDH1/2 glioma. Smaller tumor volume was associated with a lower seizure rate. Since treatment with vorasidenib also leads to gradual tumor shrinkage, these results suggest a potential mechanism of seizure control by tumor size reduction with vorasidenib.

BACKGROUND:Adolescents and young adults (AYA, 18-39) with high-grade glioma (HGG) face unique challenges at a life stage focused on autonomy, careers, relationships, and family planning. AIM:This study explores their experiences to inform life-stage appropriate support and resources. METHODS:In this mixed-methods study, we surveyed AYA HGG patients at Princess Margaret Cancer Centre (PM) to assess symptom experiences and care satisfaction. Interviews further explored their illness experiences and needs. Descriptive statistics summarized survey data, and thematic analysis guided by Braun and Clarke's framework identified key interview themes. Triangulation compared survey and interview results for a comprehensive understanding. RESULTS:Seventeen participants (7 men, 10 women; mean age 30.57) completed surveys and interviews. Triangulation revealed typical AYA challenges, such as delays in education, careers, and relationships, along with HGG-specific issues. Three main themes emerged: (1) managing cognitive and treatment-related impacts on life goals, (2) addressing physical and cognitive impairments affecting relationships, and (3) navigating identity loss and independence due to neurological symptoms. CONCLUSIONS:These findings highlight the need for tailored interventions and educational support integrated into AYA HGG care pathways.

Glioblastoma is the most common and aggressive malignant brain tumor in adults, with an increasing incidence and a poor prognosis. Current challenges in glioblastoma management include rapid tumor growth, limited treatment effectiveness, high recurrence rates, and a significant impact on patients’ quality of life. Given the complexity of glioblastoma care and recent advancements in diagnostic and treatment modalities, updated guidelines are needed in Canada. This Delphi study aimed to develop Canadian consensus recommendations for the diagnosis, classification, and management of newly diagnosed and recurrent glioblastoma. A multidisciplinary panel of 14 Canadian experts in glioblastoma care was convened, and a comprehensive literature review was conducted to synthesize evidence and formulate initial recommendations. Consensus was achieved through three Delphi rounds, in which panelists rated their agreement with recommendation statements on a five-point Likert scale. Statements with ≥75% agreement were accepted, and others were revised for re-voting. Final recommendations were formulated based on the consensus level, strength of evidence, clinical expertise, and consideration of the Canadian healthcare context. These recommendations aim to standardize glioblastoma diagnosis and classification across Canada, provide evidence-based guidance for optimal treatment selection, integrate novel therapies, and enhance the overall quality of care for glioblastoma patients.

2002 Background: The 1st and 2 nd interim analyses of the CATNON trial on anaplastic glioma (NCT00626990) showed benefit from adjuvant (adj) temozolomide (TMZ) on overall survival (OS) in patients with IDH mutant (mt) tumors, but no benefit of concurrent (conc) TMZ regardless of Isocitrate dehydrogenase 1 and 2 (IDH) mutation (mt) status. We now present the final analysis and the exploratory molecular marker analysis of the study. Methods: The 2x2 factorial design phase III CATNON trial randomized 751 adult patients with newly diagnosed non-codeleted anaplastic glioma to either 59.4 Gy radiotherapy (RT) alone; the same RT with concTMZ; the same RT and 12 cycles of adjTMZ or the same RT with both concTMZ and adjTMZ. Methylation status including MGMT promoter methylation status were assessed with the Infinium MethylationEPIC Beadchip. IDH mutation (mt) status and glioma specific alterations were assessed with a glioma targeted panel using Agilent SureSelect baits. Results: After a median follow-up of 10.9 years and with 499 events observed, in the intent-to-treat population the hazard ratio (HR) for OS adjusted for stratification factors after concTMZ was 0.906 (95%CI 0.760, 1.082; p=0.28) and after adjTMZ 0.647 (95%CI 0.541, 0.773; p <0.0001). In 660 patients IDH status could be determined: IDH was mt in 444 tumors and wild type (wt) in 216 tumors. Median OS was 1.7 yrs in patients with IDHwt tumors and 8.5 years in patients with IDHmt tumors. Benefit to TMZ was limited to patients with anaplastic glioma IDHmt of which 199 were still alive (45%). For patients with IDHmt tumors the HR for concTMZ was 0.81 (95% CI 0.63-1.04; p=0.09) and for adjTMZ 0.54 (95% CI 0.42-0.69,p < 0.0001). No benefit was observed of concTMZ in IDHmt glioma patients that also received adjTMZ (HR 0.92 95% CI 0.63-1.36; p=0.69). In patients with IDHmt tumors that had received any TMZ median OS was 10.3 years, the median OS in patients treated with adjTMZ was 12.5 years (95% CI 9.4-15.0; p<0.0001). In exploratory analysis, high-copy number Amplification of PDGFR and CDK4 ; Homozygous deletion of the CDKN2A/B locus, total copy number alterations, methylation subtype (A_IDH vs A_IDH_HG, G-CIMP high versus low, MGMT -promoter methylation as determined by methylation arrays) were all associated with outcome but none was predictive for benefit to TMZ. Conclusions: Despite more follow-up, concTMZ did not improve OS regardless of IDH status. AdjTMZ increased OS in patients with IDHmt tumors but not in patients with IDHwt tumors. Molecular factors of known prognostic significance for IDHmt 1p/19q intact anaplastic glioma did not predict benefit to TMZ. Median OS in patients with IDHmt glioma having received adjTMZ after RT was 12.5 years. Standard of post-operative care in patients with high grade IDHmt astrocytoma should be RT followed by 12 cycles adjTMZ. Funding Source: MSD. Clinical trial information: NCT00626990 .

Post-operative prognostication in glioma patients remains a clinical challenge, particularly given the heterogeneity in tumor biology and patient outcomes. We evaluated whether image-derived features from post-operative imaging improve survival modeling beyond established clinicopathologic factors. We analyzed a cohort of 71 post-surgical glioma patients treated at Princess Margaret Cancer Centre with known clinicopathologic features including age, histological classification, IDH mutation status, MGMT methylation status, extent of resection, and performance status. A baseline Cox proportional hazards model was fit to clinical variables. Radiomic features were extracted using PyRadiomics from post-operative CT and MRI across three regions of interest: whole brain, tumor bed, and peritumoral ring. Features underwent stepwise unsupervised reduction (variance filtering, exclusion of volume-correlated features, and removal of remaining collinear features), followed by dimensionality reduction via principal component analysis. Combined clinical and imaging models were evaluated in the overall cohort and stratified by IDH mutation status. In the overall cohort, the clinical model was highly prognostic (C-index 0.74, p ~ 3.2×10⁻⁶). Adding imaging features improved performance (C-index 0.79) but was not significant (p ~ 0.31). Subset analysis revealed differential effects by IDH status. In IDH-mutant gliomas (n=24), neither clinical nor combined models were significant. In IDH wild-type glioblastoma (n=47), the clinical model achieved C-index 0.75 (p=0.04). The addition of imaging features significantly improved model performance (C-index 0.83, p=0.03), with selected imaging components contributing independent prognostic value after adjustment for clinical variables. Post-hoc analysis of radiomic feature importance (random forest ranking) revealed that top contributing features were drawn from both CT and MRI modalities, with most sourced from the whole brain region. In post-surgical patients with IDH wild-type glioblastoma, image-derived features from post-operative imaging can significantly enhance prognostic modeling beyond known clinicopathologic factors. These preliminary findings support the potential role of radiomic biomarkers in refining risk stratification for this patient subgroup.

2000 Background: The 1st interim analysis of the CATNON trial showed benefit from adjuvant (adj) temozolomide (TMZ) on overall survival (OS) but remained inconclusive about concurrent (conc) TMZ. A 2 nd interim analysis was planned after 356 events. Methods: The 2x2 factorial design phase III CATNON trial randomized 751 adult patients with newly diagnosed non-codeleted anaplastic glioma to either 59.4 Gy radiotherapy (RT) alone; the same RT with concTMZ; the same RT and 12 cycles of adjTMZ or the same RT with both concTMZ and adjTMZ ( doi: 10.1016/S0140-6736(17)31442-3). MGMT promoter methylation ( MGMTmeth) status was re-assessed with the Infinium Methylation EPIC Beadchip using the MGMT_STP27 model. Isocitrate dehydrogenase 1 and 2 ( IDH) mutation (mt) status was assessed with glioma targeted Agilent SureSelect baits sequence using an Illumina HiSeq2500 Rapid PE100. Results: With a median follow-up of 56 months and 356 events, the hazard ratio (HR) for OS adjusted for stratification factors after concTMZ was 0.968 (99.1% CI 0.73, 1.28). 5-year OS was 50.2% with and 52.7% without concTMZ (95% CI [44.4, 55.7] and [46.9, 58.1]). An IDHmt was found in 335 of 480 assessed cases (70%). Median OS was 19 mo (95% CI 16.3, 22.3) in IDHwt tumors and 116 mo (95% CI 82.0, 116.6) in IDHmt tumors. HR for OS after concTMZ in patients with known IDH status. Clinical trial information: NCT00626990. IDHmt was predictive of benefit from adjTMZ ( IDHmt HR: 0.41, 95% CI 0.27, 0.64; IDHwt: HR 1.05, 95% CI 0.73, 1.52; interaction test p = 0.001). In IDHmt patients that received adjTMZ, the HR for OS after concTMZ was 0.71 (95% CI 0.35, 1.42, p=0.32). MGMTmeth was found in 288 of 410 assessed cases (70%), interaction test for concTMZ (p = 0.092) and adjTMZ (p = 0.166) did not reach statistical significance. Conclusions: In the entire study cohort, concTMZ did not increase OS. However, in IDHmt tumors a trend towards benefit of concTMZ is present. AdjTMZ increased OS in IDHmt but not in IDHwt tumors. The ongoing molecular analyses and further follow-up will allow full assessment of efficacy in the molecular subgroups.[Table: see text]

Background:This first-in-human study evaluated EGFRvIII × CD3 TCB, a novel T cell bispecific antibody, in patients with newly diagnosed EGFRvIII-positive glioblastoma. Methods:Patients with newly diagnosed glioblastoma received escalating doses of EGFRvIII × CD3 TCB following chemoradiation. The primary objectives were to evaluate safety/tolerability and define the maximum tolerated dose (MTD); secondary objectives included pharmacokinetics (PK), immunogenicity, pharmacodynamics, and clinical activity. Results:Thirty-six patients were enrolled, 32 with unmethylated and 4 with methylated MGMT promoter. EGFRvIII × CD3 TCB doses ranged from 0.004 to 10 mg Q3W, administered either on a flat or step-up dose schedule. One DLT occurred (grade 3 seizure). The MTD was not reached. Most adverse events (AEs) were of grade 1-2 severity, with headache being the most common treatment-related AE (22%). EGFRvIII × CD3 TCB showed dose-proportional PK in serum and cerebrospinal fluid (CSF), with a CSF/serum ratio of 0.08. At the highest dose tested, 10 mg Q3W, maximum serum concentrations remained 6-fold below the lower boundary of the predicted anticipated therapeutic dose. Conclusions:The administration of EGFRvIII × CD3 TCB in a maintenance setting, following standard of care treatment, was safe and well tolerated up to the highest tested dose of 10 mg Q3W. However, evidence of efficacy was not observed at the evaluated doses, suggesting that a study of higher dose levels may be warranted.