What is the Current State of ADC Treatment in EGFR-Amplified Glioblastoma?

EGFR amplification can be observed in half of the population of patients who have glioblastoma, according to Sonia Jain, PhD. For that reason, developing an antibody-drug conjugate (ADC) that targets EGFR is important, although current patient outcomes are not optimal.

During the 16th Annual World ADC Summit in San Diego, CA, Jain, a postdoctoral fellow and research associate at the Mayo Clinic in Rochester, Minnesota, presented a seminar titled, “Assessing safety & [pharmacokinetic] profiles of ADCs against glioblastoma to understand reasons for observed toxicity & explore mitigation strategies”. Following the seminar, CancerNetwork® spoke with Jain about the state of ADCs in glioblastoma.

During the discussion, she also spoke about the current state of EGFR-directed ADCs, highlighting depatuxizumab mafodotin (ABT-414), ABBV-221, and ABBV-321 as notable examples. Depatuxizumab mafodotin was evaluated in the phase 3 Intellance1 trial (NCT02573324) in patients with newly diagnosed, EGFR-amplified glioblastoma. As Jain said, this trial did not meet significance for overall survival.

Ultimately, Jain concluded by posing a single question: “What can we improve in the future?”

Transcript:

In glioblastoma, half of the population has EGFR amplification. The ADC field—this work was started 5 to 7 years ago––at that time, an ADC developed by AbbVie was targeting EGFR, and there were no good indicators of how [pharmacokinetics] looked in mouse models. [The rationale] was to improve patient outcomes…which is not great as of now.

The 3 EGFR-targeting ADCs that I have tested have been in clinical trials. [Depatuxizumab mafodotin] has been the safest. [ABBV-221] and [ABBV-321] basically showed a bit of toxicity, and the trial was stopped in phase 1.

[Depatuxizumab mafodotin] performed well in the early clinical and pre-clinical phases, but it failed to provide overall survival in the phase 3 clinical trial. That’s why it is not in the market. It’s not benefiting patients. That’s where our work most relies upon: what can we improve in the future?

References

Jain S. Assessing safety & PK profiles of ADCs against glioblastoma to understand reasons for observed toxicity & explore mitigation strategies. Presented at the 2025 World Antibody Drug Conjugate Conference; San Diego, CA; November 3-6, 2025.