Real-time customized precision combination therapies based on potential actionability and coalterations to provide therapeutic opportunities for hyperprogressive disease after immune checkpoint inhibitor therapy

e14688 Background: Patients with hyperprogressive disease (HPD) after immune checkpoint inhibitor therapies have few treatment options and short survival times. Genomic-based precision medicine within the frame of molecular tumor board might theoretically enable effective treatment identification for HPD. Detailed data on MTB guided treatments and outcome with a focus on HPD have not been reported yet. Methods: This is a single-institution retrospective, open-label, histology-agnostic analysis of the consecutively identified HPD patients that have received a real-time precision combination treatment approach which would rapidly integrate clinical grade targeted next-generation sequencing, NGS interpretation and with or without patient-derived xenografting to identify and prioritize effective customized targeted combination treatments within the frame of molecular tumor board at the Tianjin Medical University Second Hospital, a single large academic medical center, refractory cancer-foucused, between January 2018 and January 2022. Treatment was selected using on-label, off-label or investigational agents either in monotherapy or in combination. Clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, outcomes, response assessment based on radiologic imaging and follow-up data were assessed through database searching. Results: A total of 41 HPD suspected patients were referred to the MTB, and 38 conformed HPD with one of the criteria of Russo or Kato. 27 patients were treated with MTB recommended targeted mono or combinational therapy, 4 in accordance with guidelines (on label) in clinical practice, and 23 off label within two ongoing real-time precision medicine programme for patients with exhausted standard care. Of 25 evaluable patients, 20 (80%) achieved either partial response (n = 13, 52%) or stable disease (n = 7, 28%) and with a median overall survival of 12.2 months (95% CI, 8.4 months to not reached). Furthermore, 14 (56%) of those patients showed improvement in progression-free survival of at least 30% while on MTB-recommended treatment compared with the progression-free survival of the previous treatment line. Conclusions: It represents a proof of-concept case series as it demonstrates the feasibility of real time precision approach in the clinical setting and guide individual patient treatment in the rare and high aggressive disease. Patients with MTB-recommended treatments seemed to benefit with respect to PFS ratio and OS.