Mustafa Khasraw

BACKGROUND: Serclutamab talirine (Ser-T, formerly ABBV-321) is an antibody-drug conjugate consisting of an antibody (AM-1-ABT-806) directed against activated epidermal growth factor receptor (EGFR) and a pyrrolobenzodiazepine dimer. We investigated Ser-T monotherapy in a phase I, first-in-human, dose-escalation, and dose-expansion study in patients with advanced solid tumors associated with EGFR overexpression. METHODS: Eligible patients (≥18 years) had advanced, histologically confirmed solid tumors associated with EGFR overexpression (centralized testing). Patients received Ser-T intravenously once every 4 weeks (Q4W; 5-50 μg/kg) in the dose-escalation phase. Herein, preliminary antitumor activity at the recommended phase II dose (RP2D) is reported only for patients with glioblastoma (n = 24); additional assessments included all treated patients. RESULTS: Sixty-two patients (median age: 58 years) were enrolled within the dose-escalation (n = 43) and dose-expansion (n = 19) phases. One dose-limiting toxicity, grade 3 aspartate aminotransferase and alanine aminotransferase elevation, occurred at 20 μg/kg during dose escalation. The Ser-T RP2D regimen of 50 μg/kg × 1 (loading dose) followed by 25 μg/kg Q4W (maintenance dose) was administered during dose expansion. Fatigue (37%) was the only treatment-emergent adverse event (AE) occurring in >25% of patients. Two patients (3%) reported mild treatment-related ocular AEs (eye pruritus). Responses in patients with glioblastoma included 1 partial response (~33 months), 6 stable disease, and 14 progressive disease (not evaluable: n = 3). CONCLUSIONS: Ser-T monotherapy at doses up to 50 μg/kg initial dose, followed by 25 μg/kg Q4W demonstrated a tolerable safety profile with minimal antitumor activity observed in patients with glioblastoma. The glioblastoma dose-expansion cohort was closed due to a lack of efficacy (NCT03234712).

Surviving cancer in the precision era of targeted drugs and immunotherapies increasingly involves surviving-with malignancy. Against this backdrop of precision, innovation and chronicity, this paper offers a person-centred examination of some of the emerging intersections of chronic living and cancer treatment. Using a temporally extended qualitative methodology drawing on solicited diaries and successive in-depth interviews with people receiving precision cancer therapies, we focus on the often opaque worlds of surviving-with cancer, day-to-day, amidst the evolving scene of therapeutic innovation. Tracing how elements of the catastrophic and the mundane are braided through these everyday experiences, we seek to provide an embodied and temporally extended account of everyday life, beyond the binaries of presence/absence of disease, or of death/cure. In so doing, we consider how the normative expectations of treatment, bodies, care and emotions are being reshaped, elevating the moral work of the precision-cancer intersection.