A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors.
| Autor: | Moreno L; Hospital Universitari Vall d'Hebron, Barcelona, Spain., Teira P; Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada., Croop JM; Division of Hematology and Oncology, Riley Hospital for Children, Indianapolis, IN, United States., Gerber NU; Department of Oncology, University Children's Hospital, Zurich, Switzerland., André N; SMARTC Unit Centre de Recherche en Cancérologie de Marseille, Inserm U1068, Aix Marseille University, Marseille, France.; Service d'Hématologie & Oncologie Pédiatrique, Timone Hospital, AP-HM, Marseille, France., Aerts I; Institut Curie, Paris, France., Gros Subias L; Hospital Universitari Vall d'Hebron, Barcelona, Spain., De Wilde B; Universitair Ziekenhuis Gent, Ghent, Belgium., Bautista F; Division of Pediatric Hematology and Oncology, Hospital Universitario Niño Jesús, Madrid, Spain., Turpin B; Cincinnati Children's Hospital, Cincinnati, OH, United States., Kunduri S; Parexel, Hyderabad, Telangana, India., Hamidi A; Amgen Inc., Thousand Oaks, CA, United States., Lawrence T; Amgen Inc., Thousand Oaks, CA, United States., Streby KA; Department of Hematology/Oncology/BMT, Nationwide Children's Hospital/The Ohio State University, Columbus, OH, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in pediatrics [Front Pediatr] 2023 May 24; Vol. 11, pp. 1183295. Date of Electronic Publication: 2023 May 24 (Print Publication: 2023). |
| DOI: | 10.3389/fped.2023.1183295 |
| Abstrakt: | Background: The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non-central nervous system tumors. Methods: T-VEC was delivered by intralesional injection at 10 6 plaque-forming units (PFU)/ml on the first day, followed by 10 8 PFU/ml on the first day of week 4 and every 2 weeks thereafter. The primary objective was to evaluate the safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs). Secondary objectives included efficacy indicated by response and survival per modified immune-related response criteria simulating the Response Evaluation Criteria in Solid Tumors (irRC-RECIST). Results: Fifteen patients were enrolled into two cohorts based on age: cohort A1 ( n = 13) 12 to ≤21 years old (soft-tissue sarcoma, n = 7; bone sarcoma, n = 3; neuroblastoma, n = 1; nasopharyngeal carcinoma, n = 1; and melanoma, n = 1) and cohort B1 ( n = 2) 2 to <12 years old (melanoma, n = 2). Overall, patients received treatment for a median (range) of 5.1 (0.1, 39.4) weeks. No DLTs were observed during the evaluation period. All patients experienced at least one treatment-emergent adverse event (TEAE), and 53.3% of patients reported grade ≥3 TEAEs. Overall, 86.7% of patients reported treatment-related TEAEs. No complete or partial responses were observed, and three patients (20%) overall exhibited stable disease as the best response. Conclusions: T-VEC was tolerable as assessed by the observation of no DLTs. The safety data were consistent with the patients' underlying cancer and the known safety profile of T-VEC from studies in the adult population. No objective responses were observed. Trial Registration: ClinicalTrials.gov: NCT02756845. https://clinicaltrials.gov/ct2/show/NCT02756845. Competing Interests: •Lucas Moreno: Data monitoring committees for clinical trials sponsored by Novartis, Actuate Therapeutics, Shionogi, Incyte, the University of Southampton and the Royal Marsden NHS Foundation Trust; consulting for Novartis, EUSA Pharma, Norgine, Y mAbs Therapeutics, and Shionogi; travel expenses by EUSA Pharma; educational activities by Bayer and EUSA Pharma; drugs provided for academic trials by Roche Genentech and EUSA Pharma; member of the Executive Committee of SIOPEN (European neuroblastoma research cooperative group), which receives royalties for the sales of dinutuximab beta.•Pierre Teira: no disclosures.•James M. Croop: no disclosures.•Nicolas U. Gerber: no disclosures.•Nicolas André: advisory boards for BMS, Bayer, and Partner Therapeutics; travel grants from BMS; drugs provided for academic clinical trials by BMS and Pierre Fabre; grants for academic clinical trials from BMS.•Isabelle Aerts: advisory boards for AstraZeneca; travel grants from BMS, Novartis, and Roche.•Luis Gros Subias: no disclosures.•Bram De Wilde: advisory board member for Novartis, Bayer, and Roche.•Francisco Bautista: member of a data monitoring committee for a clinical trial sponsored by Sanofi; consultant or advisory role for Bayer, Amgen, Roche Genentech, and EUSA Pharma; honoraria from Roche Genentech for speaking at symposia.•Brian Turpin: no disclosures.•Srinivasa Kunduri: employee of Parexel and working for Amgen.•Ali Hamidi: employee and stockholder of Amgen.•Tatiana Lawrence: employee and stockholder of Amgen.•Keri A. Streby: consulting work with Amgen, Y-mAbs Therapeutics, and Illumina Radiopharmaceuticals LLC. (© 2023 Moreno, Teira, Croop, Gerber, André, Aerts, Gros Subias, De Wilde, Bautista, Turpin, Kunduri, Hamidi, Lawrence and Streby.) |
| Databáze: | MEDLINE |
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