Jonathan Benjamin Gill

Due to the paucity of validated cell-surface osteosarcoma-specific targets, patients with this condition have long been excluded from the benefits of antibody–drug conjugate (ADC) therapy observed in patients with several solid and hematologic malignancies. Our comprehensive surfaceome profiling approach previously identified osteosarcoma-specific cell-surface antigens that are highly expressed in osteosarcomas but minimally expressed in normal tissues. As a result, one such antigen, CADM1, was selected for the generation of an ADC. We tested a CADM1-targeting ADC with a tesirine payload (SG3249) in vitro in osteosarcoma, rhabdomyosarcoma, and neuroblastoma patient-derived xenograft (PDX) cell lines. In vivo, we tested six CADM1-expressing osteosarcoma PDX models. The CADM1 ADC demonstrated significant antitumor activity in vitro across the osteosarcoma, rhabdomyosarcoma, and neuroblastoma cell lines. Additionally, it effectively reduced tumor volume and extended event-free survival in all six osteosarcoma PDX models tested. Notably, the CADM1 ADC achieved a major complete response in one model (OS2), complete responses in two models (OS1 and OS33), and partial responses in three models (OS9, OS17, and OS31). Based on these results, clinical development of CADM1-targeted therapies for osteosarcoma and other CADM1-expressing pediatric solid tumors may be warranted.

Due to the paucity of validated cell-surface osteosarcoma-specific targets, patients with this condition have long been excluded from the benefits of antibody–drug conjugate (ADC) therapy observed in patients with several solid and hematologic malignancies. Our comprehensive surfaceome profiling approach previously identified osteosarcoma-specific cell-surface antigens that are highly expressed in osteosarcomas but minimally expressed in normal tissues. As a result, one such antigen, CADM1, was selected for the generation of an ADC. We tested a CADM1-targeting ADC with a tesirine payload (SG3249) in vitro in osteosarcoma, rhabdomyosarcoma, and neuroblastoma patient-derived xenograft (PDX) cell lines. In vivo, we tested six CADM1-expressing osteosarcoma PDX models. The CADM1 ADC demonstrated significant antitumor activity in vitro across the osteosarcoma, rhabdomyosarcoma, and neuroblastoma cell lines. Additionally, it effectively reduced tumor volume and extended event-free survival in all six osteosarcoma PDX models tested. Notably, the CADM1 ADC achieved a major complete response in one model (OS2), complete responses in two models (OS1 and OS33), and partial responses in three models (OS9, OS17, and OS31). Based on these results, clinical development of CADM1-targeted therapies for osteosarcoma and other CADM1-expressing pediatric solid tumors may be warranted.

Treemap of most common drug mechanisms for patients treated in biomarker-matched studies.

Summary of response outcomes across subgroups

Introduction Empathic communication is crucial for clinicians when discussing palliative and end-of-life (PC/EOL) care with parents of children with cancer. Unfortunately, many parents report inadequate communication at these distressing times. This study evaluates the communication skills training (CST) clinicians received to deliver a PC/EOL communication intervention as part of a multi-site randomized-controlled trial (RCT). Training was provided using an in-person format and then adapted to a virtual platform to accommodate remote learners. Methods Clinicians were trained in dyads (one physician and one nurse [RN] or advanced practice provider [APP]) over 3 days (in-person or virtually). Four pediatric oncology cases were developed and each incorporated three timepoints: diagnosis, disease progression, and end-of life. Training was adapted from VitalTalkTM and included didactic instruction, videos, visual aids, and role play. Participants completed a confidential, post-training survey. A self-reported quality assurance checklist measured fidelity to the intervention during the RCT. Results Thirty clinicians completed training; 26 completed post-training surveys including 46.1% physicians, 30.8% RNs and 23.1% APPs. Most were female (65.4%); white (80.8%), and 40-50 years old (53.9%). Nine (34.6%) trained in-person; the rest trained virtually. Ninety-two percent reported the course was valuable/very valuable for developing PC/EOL communication skills and 96% learned something new. Dyads trained virtually had similar fidelity to those trained in-person (95% and 90% respectively) when delivering the intervention to parents. Discussion This PC/EOL CST, implemented in-person and virtually, was valuable for improving pediatric oncology clinicians’ communication skills and was translated effectively into practice.