ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment.

Abstract

BACKGROUND:

ONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to an immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcomes.

METHODS:

In this open-label, randomized study, patients with unresectable MPM received intratumoral ONCOS-102 (3×1011 virus particles on days 1, 4, 8, 36, 78, and 120) and pemetrexed plus cisplatin/carboplatin (from day 22), or pemetrexed plus cisplatin/carboplatin alone. The primary endpoint was safety. Overall survival (OS), progression-free survival, objective response rate, and tumor immunologic activation (baseline and day 36 biopsies) were also assessed.

RESULTS:

In total, 31 patients (safety lead-in: n=6, randomized: n=25) were enrolled. Anemia (15.0% and 27.3%) and neutropenia (40.0% and 45.5%) were the most frequent grade ≥3 adverse events (AEs) in the ONCOS-102 (n=20) and chemotherapy-alone (n=11) cohorts. No patients discontinued ONCOS-102 due to AEs. No statistically significant difference in efficacy endpoints was observed. There was a numerical improvement in OS (30-month OS rate 34.1% vs 0; median OS 20.3 vs 13.5 months) with ONCOS-102 versus chemotherapy alone in chemotherapy-naïve patients (n=17). By day 36, ONCOS-102 was associated with increased T-cell infiltration and immune-related gene expression that was not observed in the control cohort. Substantial immune activation in the tumor microenvironment was associated with survival at month 18 in the ONCOS-102 cohort.

CONCLUSIONS:

ONCOS-102 plus pemetrexed and cisplatin/carboplatin was well tolerated by patients with MPM. In injected tumors, ONCOS-102 promoted a proinflammatory environment, including T-cell infiltration, which showed association with survival at month 18.

• Authors: Santiago Ponce, Susana Cedrés, Charles Ricordel, Nicolas Isambert, Santiago Viteri, Mercedes Herrera-Juarez, Alex Martinez-Marti, Alejandro Navarro, Mathieu Lederlin, Xavier Serres, Jon Zugazagoitia, Sylvia Vetrhus, Magnus Jaderberg, Thomas Birkballe Hansen, Victor Levitsky, Luis Paz-Ares
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 11 Issue 9 (09 2023) ISSN: 2051-1426 [Electronic] England
• PMID: 37661097 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Pemetrexed
• Platinum
• Cisplatin
• Carboplatin

Topics

• Humans
• Pemetrexed (pharmacology, therapeutic use)
• Platinum
• Mesothelioma, Malignant
• Cisplatin
• Tumor Microenvironment
• Carboplatin