A Phase 1 Safety Study of Avelumab Plus Stereotactic Body Radiation Therapy in Malignant Pleural Mesothelioma

Andreas Rimner, MD; Prasad S. Adusumilli, MD; Michael D. Offin, MD; Stephen B. Solomon, MD; Etay Ziv, MD; Sara A. Hayes, MD; Michelle S. Ginsberg, MD; Jennifer L. Sauter, MD; Daphna Y. Gelblum, MD; Annemarie F. Shepherd, MD; David M. Guttmann, MD; Jordan E. Eichholz, MS; Zhigang Zhang, PhD; Erika Ritter, BS; Phillip Wong, PhD; Afsheen N. Iqbal, MD; Robert M. Daly, MD; Azadeh Namakydoust, MD; Henry Li, BS; Megan McCune, BS; Emily H. Gelb, BS; Neil K. Taunk, MD; Donata von Reibnitz, MD; Neelam Tyagi, PhD; Ellen D. Yorke, PhD; Valerie W. Rusch, MD; Marjorie G. Zauderer, MD

JTO Clinical and Research Reports (Jan 2023)

A Phase 1 Safety Study of Avelumab Plus Stereotactic Body Radiation Therapy in Malignant Pleural Mesothelioma

Andreas Rimner, MD,
Prasad S. Adusumilli, MD,
Michael D. Offin, MD,
Stephen B. Solomon, MD,
Etay Ziv, MD,
Sara A. Hayes, MD,
Michelle S. Ginsberg, MD,
Jennifer L. Sauter, MD,
Daphna Y. Gelblum, MD,
Annemarie F. Shepherd, MD,
David M. Guttmann, MD,
Jordan E. Eichholz, MS,
Zhigang Zhang, PhD,
Erika Ritter, BS,
Phillip Wong, PhD,
Afsheen N. Iqbal, MD,
Robert M. Daly, MD,
Azadeh Namakydoust, MD,
Henry Li, BS,
Megan McCune, BS,
Emily H. Gelb, BS,
Neil K. Taunk, MD,
Donata von Reibnitz, MD,
Neelam Tyagi, PhD,
Ellen D. Yorke, PhD,
Valerie W. Rusch, MD,
Marjorie G. Zauderer, MD

Affiliations

Andreas Rimner, MD: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York; Corresponding author. Address for correspondence: Andreas Rimner, MD, Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 530 East 74th Street, New York, NY 10021.
Prasad S. Adusumilli, MD: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Michael D. Offin, MD: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Stephen B. Solomon, MD: Department of Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Etay Ziv, MD: Department of Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Sara A. Hayes, MD: Department of Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Michelle S. Ginsberg, MD: Department of Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Jennifer L. Sauter, MD: Department of Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Daphna Y. Gelblum, MD: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Annemarie F. Shepherd, MD: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
David M. Guttmann, MD: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Jordan E. Eichholz, MS: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Zhigang Zhang, PhD: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Erika Ritter, BS: Department of Immune Monitoring Core Facility, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Phillip Wong, PhD: Department of Immune Monitoring Core Facility, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Afsheen N. Iqbal, MD: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Robert M. Daly, MD: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Azadeh Namakydoust, MD: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Henry Li, BS: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Megan McCune, BS: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Emily H. Gelb, BS: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Neil K. Taunk, MD: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Donata von Reibnitz, MD: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Neelam Tyagi, PhD: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Ellen D. Yorke, PhD: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Valerie W. Rusch, MD: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
Marjorie G. Zauderer, MD: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York

Journal volume & issue: Vol. 4, no. 1
p. 100440

Abstract

Read online

Introduction: Single-agent monoclonal antibody therapy against programmed death-ligand 1 (PD-L1) has modest effects in malignant pleural mesothelioma. Radiation therapy can enhance the antitumor effects of immunotherapy. Nevertheless, the safety of combining anti-PD-L1 therapy with stereotactic body radiation therapy (SBRT) is unknown. We present the results of a phase 1 trial to evaluate the safety of the anti-PD-L1 antibody avelumab plus SBRT in patients with malignant pleural mesothelioma. Methods: This was a single-arm, investigator-initiated trial in patients who progressed on prior chemotherapy. Avelumab was delivered every other week, and SBRT was delivered to one lesion in three to five fractions (minimum of 30 Gy) followed by continuation of avelumab up to 24 months or until disease progression. The primary end point of the study was safety on the basis of grade 3+ nonhematologic adverse events (AEs) within 3 months of SBRT. Results: Thirteen assessable patients received a median of seven cycles (range: 2–26 cycles) of avelumab. There were 27 grade 1, 17 grade 2, four grade 3, and no grade 4 or 5 avelumab-related AEs. The most common were infusion-related allergic reactions (n = 6), anorexia or weight loss (n = 6), fatigue (n = 6), thyroid disorders (n = 5), diarrhea (n = 3), and myalgia or arthralgias (n = 3). There were 10 grade 1, four grade 2, one grade 3, and no grade 4 or 5 SBRT-related AEs. The most common were diarrhea (n = 3), chest pain/myalgia (n = 2), fatigue (n = 2), cough (n = 2), dyspnea (n = 2), and nausea/vomiting (n = 2). Conclusions: Combination avelumab plus SBRT seems tolerable on the basis of the prespecified toxicity end points of the first stage of this Simon two-stage design phase 1 study.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

About the journal

Abstract

Keywords