| Added by | mollevi |
|---|---|
| Last modified by | amaraver |
| Group name | EquipeAM |
| Item Type | Journal Article |
| Title | Safety and immunogenicity of the PRAME cancer immunotherapeutic in patients with resected non-small cell lung cancer: a phase I dose escalation study |
| Creator | Pujol et al. |
| Author | J. L. Pujol |
| Author | T. De Pas |
| Author | A. Rittmeyer |
| Author | E. Vallieres |
| Author | B. Kubisa |
| Author | E. Levchenko |
| Author | S. Wiesemann |
| Author | G. A. Masters |
| Author | R. Shen |
| Author | S. A. Tjulandin |
| Author | H. S. Hofmann |
| Author | N. Vanhoutte |
| Author | B. Salaun |
| Author | M. Debois |
| Author | S. Jarnjak |
| Author | P. M. De Sousa Alves |
| Author | J. Louahed |
| Author | V. G. Brichard |
| Author | F. F. Lehmann |
| Abstract | INTRODUCTION: Adjuvant platinum-based chemotherapy is standard treatment for surgically resected stage II-IIIA non-small cell lung cancer (NSCLC), but the relapse rate is high. The PRAME tumor antigen is expressed in two-thirds of NSCLC, and offers an attractive target for antigen-specific immunization. A Phase I dose-escalation study assessed the safety and immunogenicity of the PRAME immunotherapeutic in patients with surgically resected NSCLC (NCT01159964). METHODS: Patients with PRAME-positive resected stage IB-IIIA NSCLC were enrolled in three consecutive cohorts to receive up to 13 injections of PRAME immunotherapeutic (recombinant PRAME protein dose 20mug, 100mug or 500mug) with AS15 immunostimulant. Adverse events (AEs), pre-defined dose-limiting toxicity (DLT), and the anti-PRAME humoral response (measured by ELISA), were co-primary endpoints. Anti-PRAME cellular responses were assessed. RESULTS: 60 patients were treated (18 received 20mug PRAME, 18 received 100mug PRAME, 24 received 500mug PRAME). No DLT was reported. AEs considered by the investigator to be causally related to treatment were grade 1 or 2, and most were injection site reactions or fever. All patients had detectable anti-PRAME antibodies after four immunizations. Percentages of patients with PRAME-specific CD4+ T-cells were higher at the 500mug dosage compared with lower dosages. No pre-defined CD8+ T-cell responses were detected. CONCLUSION: The PRAME immunotherapeutic had an acceptable safety profile. All patients had anti-PRAME humoral responses that were not dose-related, and 80% treated at the highest dose showed a cellular immune response. The 500mug dose was selected. However, further development was stopped after negative results with a similar immunotherapeutic in patients with NSCLC. |
| Publication | J Thorac Oncol |
| Date | Aug 17 2016 |
| Journal Abbr | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer |
| DOI | 10.1016/j.jtho.2016.08.120 |
| ISSN | 1556-1380 (Electronic) 1556-0864 (Linking) |
| Tags | clinic |
| Date Added | 2018/11/14 - 12:43:03 |
| Date Modified | 2019/05/16 - 11:01:32 |
| Notes and Attachments | (Note) (Note) (Note) 27544054 (Attachment) |
Institut de Recherche en Cancérologie de
