GBM is the most common primary brain tumor. Survival is poor with standard surgery followed by radiotherapy (RT) and temozolomide (TMZ). Pseudo-progression on MRI is well described post-RT, particularly within the first 3 months, and confounds response assessment. Whilst not previously described for drug treatment alone, anecdotal cases were described in a Phase 1 study of depatuxizumab mafodotin (depatux-m). Depatux-m is an antibody-drug conjugate, comprised of a tumor-specific anti-EGFR antibody linked to a microtubule cytotoxin, monomethyl auristatin F, that demonstrated promising antitumor activity in adult GBM pts with EGFR-amplified tumors. This exploratory study will determine if depatux-m exhibits radiologically evident treatment effects in pts with GBM, i.e. drug induced pseudo-progression.
This non-interventional study enrolls pts with GBM who underwent tumor debulking surgery after MRI evidence suggested treatment failure in Phase 1-3 depatux-m trials. Pts had received depatux-m alone or in combination with TMZ. Resected tumor tissue is formalin-fixed, paraffin-embedded and centrally reviewed. Radiographic assessments were collected per original study protocol (typically q8 wks), or as clinically indicated, and centrally reviewed. Clinical response is evaluated by RANO criteria. This study will assess correlation between radiographic and histologic evidence of disease progression after depatux-m treatment. Exploratory endpoints are progression-free survival and overall survival.
As of April 2018, 7 pts with recurrent GBM were enrolled at 2 sites in Australia. All pts completed RT at a minimum of 11 months (range 11-26) prior to re-resection. 4 pts had histological confirmation of recurrence prior to treatment.
Histology showed that 57% (4/7) of pts with disease progression by RANO criteria after depatux-m, with or without TMZ, had predominantly treatment effect per local pathologist assessment. Central review indicated that of these 4 pts, 2 pts were ≥75% necrotic and 2 showed complete absence of tumour. 2 pts had histological confirmation of recurrence prior to treatment. Cases and associated clinical impact are presented.
Clinical trial identification
Legal entity responsible for the study
Medical writing support was provided by Ana Mrejeru, Ph.D., of AbbVie.
H.K. Gan: Consulting/advisory role: AbbVie; Speakers’ bureau: Ignyta, Bristol-Myers Squibb; Research funding: AbbVie; Travel, accommodations, expenses: Ignyta. E. Kennedy, D. Maag: Employee and stock: AbbVie. All other authors have declared no conflicts of interest.