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NCT02756845

Study of Talimogene Laherparepvec In Children With Advanced Non CNS Tumors

Completed Phase 1 Results posted Last updated 20 February 2024
What this trial tests

Phase 1 trial testing Talimogene Laherparepvec in Advanced Non CNS Tumors in 15 participants. Completed in 29 November 2022.

Timeline
16 August 2017
Primary endpoint
17 January 2022
29 November 2022

Quick facts

Lead sponsorAmgen
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment15
Start date16 August 2017
Primary completion17 January 2022
Estimated completion29 November 2022
Sites22 locations across France, Italy, Belgium, Canada, Switzerland, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Amgen — full company profile →

Who can join

Adults 2 to 21, any sex, with Advanced Non CNS Tumors. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Who Experienced a Dose-limiting Toxicity (DLT) Primary · Day 1 to Day 35

All toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0: * Grade 1: Mild * Grade 2: Moderate * Grade 3: Severe/medically significant but not immediately life-threatening * Grade 4: Life-threatening * Grade 5: Death related to adverse event The occurrence of any of the below was considered a DLT, if judged to be related to talimogene laherparepvec: * Grade 4 non-hematologic toxicity * Grade 3 non-hematologic toxicity that lasted \> 3 days despite optimal supportive care * Any ≥ grade 3 non-hematologic laboratory value if medical intervention was requir

Experienced a DLT
GroupValue95% CI
Cohort A1: Talimogene Laherparepvec (TVEC) - Aged 12 to ≤ 21 Years0.00.0 – 28.5
Cohort B1: Talimogene Laherparepvec (TVEC) - Aged 2 to < 12 Years0.00.0 – 84.2
Did Not Experience a DLT
GroupValue95% CI
Cohort A1: Talimogene Laherparepvec (TVEC) - Aged 12 to ≤ 21 Years100.071.5 – 100.0
Cohort B1: Talimogene Laherparepvec (TVEC) - Aged 2 to < 12 Years100.015.8 – 100.0
Overall Response Rate (ORR) Secondary · Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months

ORR was defined as the percentage of participants who experienced either complete response (CR) or partial response (PR) per modified immune-related response criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST) response criteria. CR was defined as the disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defin

GroupValue95% CI
Cohort A1: Talimogene Laherparepvec (TVEC) - Aged 12 to ≤ 21 Years0.00.00 – 24.71
Cohort B1: Talimogene Laherparepvec (TVEC) - Aged 2 to < 12 Years0.00.00 – 84.19
Duration of Response (DOR) Secondary · Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months

DOR was defined as the time from the date of an initial response of CR or PR to the earlier of PD/death.

GroupValue95% CI
Cohort A1: Talimogene Laherparepvec (TVEC) - Aged 12 to ≤ 21 YearsNANA – NA
Cohort B1: Talimogene Laherparepvec (TVEC) - Aged 2 to < 12 YearsNANA – NA
Time to Response (TTR) Secondary · Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months

TTR was defined as the number of days from the first dose of talimogene laherparepvec to the first objective assessment of response as per modified irRC-RECIST.

GroupValue95% CI
Cohort A1: Talimogene Laherparepvec (TVEC) - Aged 12 to ≤ 21 YearsNANA – NA
Cohort B1: Talimogene Laherparepvec (TVEC) - Aged 2 to < 12 YearsNANA – NA
Time to Progression (TTP) Secondary · Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months

TTP was defined as the time from the first dose of talimogene laherparepvec until objective tumor progression per irRC-RECIST. TTP was estimated using the Kaplan-Meier method.

GroupValue95% CI
Cohort A1: Talimogene Laherparepvec (TVEC) - Aged 12 to ≤ 21 Years2.500.00 – 9.0
Cohort B1: Talimogene Laherparepvec (TVEC) - Aged 2 to < 12 YearsNA1.6 – 3.5
Progression Free Survival (PFS) Secondary · Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months

PFS was defined as the time from the first dose to the earlier of disease progression per modified irRC-RECIST or death from any cause. PFS was estimated using the Kaplan-Meier method.

GroupValue95% CI
Cohort A1: Talimogene Laherparepvec (TVEC) - Aged 12 to ≤ 21 Years3.321.1 – 11.6
Cohort B1: Talimogene Laherparepvec (TVEC) - Aged 2 to < 12 Years6.421.6 – 11.2
Overall Survival (OS) Secondary · Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months

OS was defined as as the time from first dose to the event of death from any cause. OS was estimated using the Kaplan-Meier method.

GroupValue95% CI
Cohort A1: Talimogene Laherparepvec (TVEC) - Aged 12 to ≤ 21 Years9.401.1 – 54.5
Cohort B1: Talimogene Laherparepvec (TVEC) - Aged 2 to < 12 Years8.024.8 – 11.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Mortality: Day 1 until end of follow-up; The median [min, max] duration of follow-up was 9.396 [1.12, 54.51] months Adverse events: From first dose of study drug until 30 days after last dose. The median [min, max] duration of treatment was 1.18 [0.0, 9.1] months in T-VEC Cohort A1 and 2.81 [2.0, 3.6] months in T-VEC Cohort B1. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort A1: Talimogene Laherparepvec (TVEC) - Aged 12 to ≤ 21 Years
Serious: 5/13 (38%)
Deaths: 12/13
Cohort B1: Talimogene Laherparepvec (TVEC) - Aged 2 to < 12 Years
Serious: 1/2 (50%)
Deaths: 2/2

Serious adverse events (11 terms)

ReactionSystemCohort A1: Talimogene Lahe…Cohort B1: Talimogene Lahe…
NauseaGastrointestinal disorders
Vascular device infectionInfections and infestations
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Skin ulcerSkin and subcutaneous tissue disorders
Metastatic malignant melanomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Osteosarcoma metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhageNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Cranial nerve disorderNervous system disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Hypovolaemic shockVascular disorders
Other adverse events (69 terms — click to expand)

ReactionSystemCohort A1: Talimogene Lahe…Cohort B1: Talimogene Lahe…
PyrexiaGeneral disorders
VomitingGastrointestinal disorders
HeadacheNervous system disorders
FatigueGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Influenza like illnessGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
Sinus tachycardiaCardiac disorders
Abdominal pain upperGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Dry mouthGastrointestinal disorders
NauseaGastrointestinal disorders
AstheniaGeneral disorders
Injection site painGeneral disorders
Oedema peripheralGeneral disorders
InfluenzaInfections and infestations
Gamma-glutamyltransferase increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
ParaesthesiaNervous system disorders
CoagulopathyBlood and lymphatic system disorders
TachycardiaCardiac disorders
Autoimmune hypothyroidismEndocrine disorders
Abdominal painGastrointestinal disorders
Chest painGeneral disorders
ChillsGeneral disorders
Face oedemaGeneral disorders
Injection site inflammationGeneral disorders
MalaiseGeneral disorders
Drug hypersensitivityImmune system disorders
MastitisInfections and infestations
Nail infectionInfections and infestations
RhinitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Heat crampsInjury, poisoning and procedural complications
Procedural painInjury, poisoning and procedural complications
Wound dehiscenceInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders

Most-reported serious reactions: Nausea, Vascular device infection, Musculoskeletal chest pain, Pulmonary embolism, Skin ulcer, Metastatic malignant melanoma, Osteosarcoma metastatic, Tumour haemorrhage.

Data from ClinicalTrials.gov NCT02756845 adverse events section.

Sponsor's own description

This is a phase 1 study to evaluate the safety of intralesional talimogene laherparepvec administration in pediatric subjects with advanced non-CNS tumors that are amenable to direct injection

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Oncolytic Herpes Simplex Virus-Based Therapies for Cancer.
    Aldrak N, Alsaab S, Algethami A, Bhere D, et al · · 2021 · cited 61× · PMID 34207386 · DOI 10.3390/cells10061541
  2. Trial Watch: Oncolytic viro-immunotherapy of hematologic and solid tumors.
    Pol JG, Lévesque S, Workenhe ST, Gujar S, et al · · 2018 · cited 61× · PMID 30524901 · DOI 10.1080/2162402x.2018.1503032
  3. HSV-1 Oncolytic Viruses from Bench to Bedside: An Overview of Current Clinical Trials.
    Koch MS, Lawler SE, Chiocca EA. · · 2020 · cited 49× · PMID 33255871 · DOI 10.3390/cancers12123514
  4. Herpes simplex virus 1 as an oncolytic viral therapy for refractory cancers.
    Scanlan H, Coffman Z, Bettencourt J, Shipley T, et al · · 2022 · cited 24× · PMID 35965554 · DOI 10.3389/fonc.2022.940019
  5. Current Immunotherapeutic Strategies to Enhance Oncolytic Virotherapy.
    Meyers DE, Wang AA, Thirukkumaran CM, Morris DG. · · 2017 · cited 23× · PMID 28634571 · DOI 10.3389/fonc.2017.00114
  6. Immunotherapeutic Challenges for Pediatric Cancers.
    Hutzen B, Ghonime M, Lee J, Mardis ER, et al · · 2019 · cited 22× · PMID 31650024 · DOI 10.1016/j.omto.2019.08.005
  7. 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.
    Moreno L, Teira P, Croop JM, Gerber NU, et al · · 2023 · cited 8× · PMID 37292376 · DOI 10.3389/fped.2023.1183295
  8. Translation of oncolytic viruses in sarcoma.
    Robinson SI, Rochell RE, Penza V, Naik S. · · 2024 · cited 7× · PMID 39040851 · DOI 10.1016/j.omton.2024.200822

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