EP101-56 Co-Presentation of Adenocarcinoma and Squamous Cell Lung Carcinoma Harbouring ALK Rearrangement in Different Sites

We describe an unique case of co-presentation of ADC and SCC in two different disease sites, both harbouring ALK rearrangement. A 57-year-old male never smoker presented with a left adrenal mass. CT Scan showed a right superior lobe mass, bilateral pulmonary nodules (Fig. 1 A), and bone metastases. The lung biopsy documented ADC with moderate differentiation and ALK rearrangement by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The patient was treated with Crizotinib but, after 4 months, the CT showed a near complete response of the pulmonary disease (Fig. 1 B), while a progression of the left adrenal metastasis was observed. (Fig. 2 A, Fig. 2B). A left adrenal biopsy showed a SCC histology, with ALK rearrangement confirmed both by IHC and FISH. The treatment was switched to alectinib without respoinse so the patient received chemotherapy. The absence of an initial biopsy of the adrenal mass doesn't allow to distinguish between a lung ADC to SCC transdiffere..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2028

Authors: V. Longo, A. Catino, D. Galetta, G. Del Bene, R. Lacalamita, M. Montrone, F. Pesola, D. Petriella, P. Pizzutilo, S. Tommasi

Conference PaperKirk SmithOctober 1, 2019ADC, SCC, ALK rearrangement

An antibody-drug conjugate directed to the ALK receptor demonstrates efficacy in preclinical models of neuroblastoma

Enthusiasm for the use of antibody-drug conjugates (ADCs) in cancer therapy has risen over the past few years. The success of this therapeutic approach relies on the identification of cell surface antigens that are widely and selectively expressed on tumor cells. Studies have shown that native ALK protein is expressed on the surface of most neuroblastoma cells, providing an opportunity for development of immune-targeting strategies. Clinically relevant antibodies for this target have not yet been developed. Here, we describe the development of an ALK-ADC, CDX-0125-TEI, which selectively targets both wild-type and mutated ALK-expressing neuroblastomas. CDX-0125-TEI exhibited efficient antigen binding and internalization, and cytotoxicity at picomolar concentrations in cells with different expression of ALK on the cell surface. In vivo studies showed that CDX-0125-TEI is effective against ALK wild-type and mutant patient-derived xenograft models. These data demonstrate that ALK is a bona fide immunotherapeutic target and provide a rationale for clinical development of an ALK-ADC approach for neuroblastomas and other ALK-expressing childhood cancers such as rhabdomyosarcomas. READ ARTICLE

Science Translational Medicine DOI: 10.1126/scitranslmed.aau9732

Authors: Renata Sano, Kateryna Krytska, Colleen E. Larmour, Pichai Raman, Daniel Martinez, Gwenda F. Ligonjay S. Lillquist, Ulisse Cucchi, Paolo Orsini, Simona Rizzi, Bruce R. Pawel, Diego Alvarado, Yael P. Mossé

Pre-ClinicalKirk SmithJune 6, 2019Neuroblastoma, ALK, ADC