BC008-1A (PD-1/TIGIT bispecific antibody) in recurrent CNS WHO grade 4 glioma: Results from a randomized phase I study.

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Background: Dual blockade of PD-1 and TIGIT may overcome T-cell exhaustion in glioma. BC008-1A is a humanized PD-1/TIGIT bispecific antibody. We report antitumor activity from two dose cohorts in recurrent CNS WHO grade 4 glioma. Methods: In this open-label, randomized phase I study, adults with histologically confirmed recurrent CNS WHO grade 4 glioma with RANO-confirmed progression after standard therapy, no surgical plan, KPS≥70, life expectancy ≥12 weeks, and ≥1 measurable intracranial lesion by RANO were randomized 1:1 to BC008-1A 900 mg or 1200 mg IV q3w (21-day cycles). Primary endpoint was safety (AEs/SAEs; TEAEs graded per NCI-CTCAE v5.0). Secondary endpoints included ORR/DCR, TTR, DOR, PFS and OS. Results: At data cutoff 22 Jan 2026, 20 patients were treated (900 mg 10; 1200 mg 10). Median age 54 years (range 21–67); IDH-wildtype 18/20. Safety: no DLTs; grade ≥3 TRAEs [16.7]%; no serious TRAEs or treatment-related deaths. Efficacy: Median follow-up 5.6 months. Overall, PR 8/20 (ORR 40%), SD 5/20, PD 7/20 (DCR 65%). ORR was 50% (900 mg) and 30% (1200 mg). Best tumor shrinkage among responders reached 96.9% (range 81.9–96.9%). Median TTR was 2.1 months (range 0.7–4.1). DOR was up to 18 weeks, with 2 responses ongoing at cutoff. PFS events occurred in 6 patients. Conclusions: BC008-1A showed manageable safety and objective responses across 900–1200 mg in recurrent grade 4 glioma, supporting further evaluation with integrated PK and biomarker analyses. Clinical trial information: NCT06773481 .