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

Lucas Moreno; Pierre Teira; James M Croop; Nicolas U Gerber; Nicolas André; Isabelle Aerts; Luis Gros Subias; Bram De Wilde; Francisco Bautista; Brian Turpin; Srinivasa Kunduri; Ali Hamidi; Tatiana Lawrence; Keri A Streby

doi:10.3389/fped.2023.1183295

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

Front Pediatr. 2023 May 24:11:1183295. doi: 10.3389/fped.2023.1183295. eCollection 2023.

Authors

Lucas Moreno¹, Pierre Teira², James M Croop³, Nicolas U Gerber⁴, Nicolas André^{5

6}, Isabelle Aerts⁷, Luis Gros Subias¹, Bram De Wilde⁸, Francisco Bautista⁹, Brian Turpin¹⁰, Srinivasa Kunduri¹¹, Ali Hamidi¹², Tatiana Lawrence¹², Keri A Streby¹³

Affiliations

¹ Hospital Universitari Vall d'Hebron, Barcelona, Spain.
² Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada.
³ Division of Hematology and Oncology, Riley Hospital for Children, Indianapolis, IN, United States.
⁴ Department of Oncology, University Children's Hospital, Zurich, Switzerland.
⁵ SMARTC Unit Centre de Recherche en Cancérologie de Marseille, Inserm U1068, Aix Marseille University, Marseille, France.
⁶ Service d'Hématologie & Oncologie Pédiatrique, Timone Hospital, AP-HM, Marseille, France.
⁷ Institut Curie, Paris, France.
⁸ Universitair Ziekenhuis Gent, Ghent, Belgium.
⁹ Division of Pediatric Hematology and Oncology, Hospital Universitario Niño Jesús, Madrid, Spain.
¹⁰ Cincinnati Children's Hospital, Cincinnati, OH, United States.
¹¹ Parexel, Hyderabad, Telangana, India.
¹² Amgen Inc., Thousand Oaks, CA, United States.
¹³ Department of Hematology/Oncology/BMT, Nationwide Children's Hospital/The Ohio State University, Columbus, OH, United States.

Abstract

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 10⁶ plaque-forming units (PFU)/ml on the first day, followed by 10⁸ 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.

Keywords: immunotherapy; non-CNS tumors; oncolytic herpes virus; pediatric solid tumor; relapsed and refractory cancer; talimogene laherparepvec.

Associated data

ClinicalTrials.gov/NCT02756845

Grants and funding

This study received funding from Amgen Inc. The funder was involved in the study design; collection, analysis, and interpretation of data; the writing of this article; and the decision to submit it for publication.