Citations

The NCCN Guidelines for Melanoma: Cutaneous provide strategies for the diagnosis, treatment, and follow-up of patients with cutaneous melanoma, which is among the most common cancers in the United States. The outcome of cutaneous melanoma is significantly influenced by stage at initial presentation. Generally, localized disease and smaller primary tumors have been associated with more favorable prognosis. Thus, the select content featured in this issue focuses on risk factors associated with cutaneous melanoma development and which should be considered during an initial assessment. These include (1) phenotypic predispositions, (2) personal medical history or comorbidities, (3) genetic predispositions, and (4) environmental factors.

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous ) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.

2505 Background: ATRC-101 monoclonal antibody targets tumor-specific ribonucleoprotein complex (RNP) and elicits anti-tumor immunity, innate and adaptive, in preclinical models. Methods: Phase 1b is evaluating ATRC-101 as monotherapy, every 3 (3M) or 2 (2M) weeks (wk), and ATRC-101 in combination with pembrolizumab (3P) in participants (pts) with advanced solid tumors. ATRC-101 target expression is determined by CAP-CLIA IHC assay. For pts described herein, pre-treatment (tx) tumor biopsies were assessed for target expression by IHC retrospectively or prospectively. Enrollment in 3M and 3P is currently open to pts who are target positive (RNP+ve) by IHC with an H-score ≥ 50. Objectives are safety (primary), PK, immunogenicity, recommended dose for expansion, activity by RECIST1.1 and biomarker analyses in pre-tx and on-tx tumors. Results: As of Nov 18th, 2022, 67 pts received ≥1 dose of ATRC-101 (median prior tx 5, range 1-12). Tumor types were colorectal (CRC, 28), ovarian (10), breast (9), melanoma (8), non-small cell lung (NSCLC, 6), head and neck squamous cell (3), urothelial (1), esophageal (1) and small bowel (1). Tx emergent adverse events (TEAEs) Grade ≥3 occurred in 22 (33%) pts and were related to ATRC-101 in 2 (3%). No tx discontinuations or dose reductions related to ATRC-101. RECIST1.1 best overall responses in efficacy evaluable 61 pts included 1 complete response (CR) in RNP+ve melanoma (3P, 10mg/kg), and 1 partial response (PR) in RNP+ve NSCLC (3M, 30mg/kg). Further, disease stabilized (SD) in 24 pts (39%) and 35 pts had disease progression (PD, 57%) with evidence of association between anti-tumor activity and target expression. Of 24 SD, 22 were in monotherapy cohorts and included 9 CRC pts with highly refractory disease. Conclusions: ATRC-101 alone and in combination with pembrolizumab continues to be well tolerated with evidence of anti-tumor activity. Interim data support ongoing enrollment of pts with RNP+ve pre-tx tumors. Updated and new data including durability of disease control will be presented. Clinical trial information: NCT04244552 . [Table: see text]

Abstract Single-positive thymocytes that successfully complete positive and negative selection must still undergo one final step, generally termed T cell maturation, before they gain functional competency and enter the long-lived T cell pool. Maturation initiates after positive selection in single-positive thymocytes and continues in the periphery in recent thymic emigrants, before these newly produced T cells gain functional competency and are ready to participate in the immune response as peripheral naive T cells. Recent work using genetically altered mice demonstrates that T cell maturation is not a single process, but a series of steps that occur independently and sequentially after positive selection. This review focuses on the changes that occur during T cell maturation, as well as the molecules and pathways that are critical at each step.