Assessment of clinical value and barriers to use of new investigational targeted agents in the community setting: A study of claudin 18.2 and zolbetuximab.

Abstract

500 Background: Rapid integration of novel agents in clinical practice can be lifesaving. However, community-based practices may experience extended adoption times, due to practical barriers. REFLECT was developed to assess new drug implementation in the community setting. Methods: REFLECT consists of a 20-minute prerecorded presentation, followed by a data-collection event for community oncologists. It was developed to evaluate and assess challenges of implementing novel targeted agents in the community practice setting. In this pilot study, awareness of zolbetuximab (zolbe), a potential first-in-class claudin 18.2 (CLDN18.2) monoclonal antibody and companion diagnostic, was assessed. Between April and August 2024, 53 data-collection events were held representing 26 states across the US. Data from 492 oncologists were recorded and analyzed. Results: Nearly half the community oncologists (47%) were not familiar with CLDN18.2 as a therapeutic target in gastric/gastroesophageal junction (G/GEJ) cancer. Awareness of zolbe data was low among community oncologists; 79% indicated they had not seen the results from the phase 3 studies. However, 96% of oncologists reported the data will at least moderately impact their treatment of CLDN18.2+ patients with metastatic (m)G/GEJ cancer. Only 40% of oncologists reported having access to CLDN18.2 testing. Uncertainty regarding availability of CLDN18.2 testing was high among oncologists in the Central US (52%), representing a significant awareness gap for CLDN18.2 testing. Opinions were divided regarding the treatment approach for CLDN18.2+, immunosensitive patients (Table). In a HER2–, CLDN18.2+ patient with mG/GEJ cancer and a combined positive score (CPS) of 10; 58.1% would recommend first-line chemotherapy (chemo) plus immunotherapy (IO) and 40.4% would recommend chemo plus zolbe. Conclusions: First-in-class targeted agents often encounter additional challenges and knowledge gaps regarding adoption in the community practice setting, particularly associated with molecular testing. Timely education on patient identification and correct utilization may accelerate adoption of new regimens, and potentially save lives. Data-sharing and -collection platforms including REFLECT can be instrumental in the identification of challenges associated with widespread and rapid implementation of novel agents in the community oncology setting. What treatment approach would you recommend in a patient with the following characteristics, if all treatments were available? mGEJ adenocarcinoma, HER2– disease, CLDN18.2+ staining in >75% of tumor cells, CPS 10. Treatment Total: N = 492% (n) Chemo mFOLFOX6 1.0 (5) CAPOX 0 (0) Chemo + IO mFOLFOX6 + IO 52.8 (260) CAPOX + IO 5.3 (26) Chemo + zolbe mFOLFOX6 + zolbe 33.9 (167) CAPOX + zolbe 6.5 (32) Other 0.4 (2)