Data from A Phase II Window of Opportunity Study of Neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 Blockade for Patients with Malignant Pleural Mesothelioma

• DOI: 10.1158/1078-0432.c.6533147
• Publication Date: 2023-04-01T05:36:16Z
• Authors: Hyun-Sung Lee; Hee-Jin Jang; Maheshwari Ramineni; Daniel Y. Wang; Daniela Ramos; Jong Min Choi; Taylor Splawn; Monica Espinoza; Michelle Almarez; Leandria Hosey; Eunji Jo; Susan Hilsenbeck; Christopher I. Amos; R. Taylor Ripley; Bryan M. Burt
• Keywords: Durvalumab; Tremelimumab; Combination therapy; Immune checkpoint

<div>AbstractPurpose:<p>We report the results of a phase II, randomized, window-of-opportunity trial neoadjuvant durvalumab versus plus tremelimumab followed by surgery in patients with resectable malignant pleural mesothelioma (MPM; NCT02592551).</p>Patients and Methods:<p>The primary objective was alteration intratumoral CD8/regulatory T cell (Treg) ratio after combination immune checkpoint blockade (ICB) therapy. Secondary exploratory objectives included other changes tumor microenvironment, survival, safety, pathologic response (PR), systemic responses.</p>Results:<p>Nine received monotherapy 11 Seventeen 20 (85%) receiving ICB underwent planned thoracotomy. Both regimens induced CD8 T-cell infiltration into MPM tumors but did not alter CD8/Treg ratios. At 34.1 months follow-up, had longer median overall survival (not reached) compared those (14.0 months). Grade ≥3 immunotoxicity occurred 8% group 27% group. Tumor PR 6 17 thoracotomy (35.3%), among which major (>90% regression) 2 (11.8%). Single-cell profiling tumor, blood, bone marrow revealed that remodeled contexture tumors; mobilized CD57<sup>+</sup> effector memory cells from to circulation; increased formation tertiary lymphoid structures were rich cells.</p>Conclusions:<p>These data indicate orchestrates <i>de novo</i> responses extend microenvironment correlate favorable clinical outcomes.</p></div>