Adaptin Bio Opens Phase 1 Trial of Brain-Penetrant Bispecific T-Cell Engager APTN-101 in Glioblastoma

Adaptin Bio, Inc. has opened enrollment in a phase 1 clinical trial evaluating APTN-101, a bispecific T-cell engager designed to treat glioblastoma (GBM), the most common and aggressive primary brain tumor in adults.¹ The study is being conducted in collaboration with Duke University, where the BRiTE (Brain Bispecific T-cell Engager) platform underlying APTN-101 was originally developed.¹

How does APTN-101 work?

APTN-101 is engineered to cross the blood-brain barrier (BBB) and selectively target EGFRvIII, a mutated form of the epidermal growth factor receptor expressed on aggressive glioma cells.¹ The BRiTE platform uses immune cell "hitchhiking" to deliver the therapeutic across the BBB, then redirects T cells to recognize and attack EGFRvIII-positive tumor cells.¹ Bispecific formats like this rely on a capability conventional antibodies don't have. As Nikki Nogal, global director of Technical and CMC for Upstream at Lonza, explained in an earlier BioPharm International^© feature on bispecific antibody development, "Conventional mAbs typically do not activate T-lymphocytes, as this is a property unique to bispecific formats," adding that therapies capable of activating T cells within the tumor microenvironment "hold potential for significant therapeutic impacts where traditional mAbs may either be lacking or have failed."² EGFRvIII itself is a well-established GBM target for T-cell engager approaches, though its expression is variable across tumors, with published estimates ranging from roughly 24% to 67% of GBM cases depending on the detection method and cohort studied.³

"Glioblastoma is a disease with a significant unmet clinical need, limited therapeutic options, and little improvement in outcomes," said Mustafa Khasraw, M.D., professor at Duke University School of Medicine, who led the preclinical development team for APTN-101 and is principal investigator of the trial. "By combining immune-based tumor targeting with enhanced delivery to the brain, APTN-101 is designed to address two major challenges in glioblastoma treatment. This first-in-human study is an important step in determining whether this approach can translate into meaningful benefit for patients."¹

What does the preclinical data show?

In preclinical studies, APTN-101 achieved more than a 7-fold increase in brain distribution compared with the EGFRvIII T-cell engager component alone, and the combination eradicated EGFRvIII-positive GBM tumors completely in 70% to 80% of treated mice across multiple aggressive disease models.¹ Adaptin also reported an excellent safety profile with minimal off-target effects in these preclinical models.¹

"Opening enrollment in the phase 1 trial is an important milestone in the clinical development of APTN-101, a potential best-in-class therapy for the treatment of glioblastoma," said Michael J. Roberts, Ph.D., president and chief executive officer of Adaptin Bio. "In preclinical studies, APTN-101 demonstrated impressive efficacy targeting glioma cells with precision, eliminating some malignant glioma tumors across multiple aggressive disease models."¹

What does the phase 1 trial involve?

The open-label, dose-escalation study will enroll up to 15 adult patients with WHO Grade IV malignant glioma that expresses EGFRvIII.¹ The primary objective is to characterize APTN-101's safety profile and maximum tolerated dose, with the primary endpoint being the proportion of patients experiencing a dose-limiting toxicity at each dose level.¹ Secondary endpoints include pharmacokinetics and objective response rate by modified Response Assessment in Neuro-Oncology (RANO) criteria, while exploratory endpoints cover cytokine changes, formation of anti-BRiTE antibodies, overall survival, and progression-free survival.¹

Why does glioblastoma need new therapies?

GBM carries a median survival of just 12 to 18 months, with only about 5% of patients surviving beyond five years. Adaptin cites these figures in describing why standard-of-care surgery, radiotherapy, and chemotherapy have not been curative and why recurrence is common.¹ The company also states that GBM accounts for approximately 15,000 new cases annually in the US, with secondary malignant brain tumors adding roughly 200,000 more cases each year.¹ Independent estimates from the American Brain Tumor Association put annual US GBM incidence somewhat lower, at more than 12,000 new cases, suggesting the scale of unmet need holds even under more conservative counts.⁴ Adaptin also cited a GBM treatment market valued at $3.02 billion in 2025, projected to reach $4.44 billion by 2030 at an 8% compound annual growth rate.¹

What's next?

Enrollment is now open at Duke, and dose-escalation will proceed under the trial's safety-focused primary endpoints before any efficacy signal, such as tumor response by modified RANO criteria, can be assessed.¹ For more on how bispecific and multispecific antibody engineering is being adapted to overcome GBM’s blood-brain barrier and antigen-heterogeneity challenges, see BioPharm International's related coverage on next-generation antibody therapeutics for glioblastoma.

References

1. Adaptin Bio, Inc. Adaptin Bio Announces Opening of Enrollment in a Phase 1 Clinical Trial Evaluating Treatment of Malignant Brain Tumors with APTN-101. Press release. Published August 20, 2026. Accessed August 21, 2026.
2. Mirasol F. Bispecific Antibodies are Moving from Research to Clinical Development. BioPharm International. Vol 35, No 6, pp 16–20. Published June 2022. Accessed August 21, 2026.
3. Padfield E, et al. The natural history of EGFR and EGFRvIII in glioblastoma patients. Summary via UT MD Anderson Cancer Center. Accessed August 2026.
4. American Brain Tumor Association. Glioblastoma (GBM). Accessed August 2026.