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NCT03064763

Study to Evaluate the Safety/ Efficacy of T-VEC in Japanese Subjects With Unresectable Stage IIIB-IV Malignant Melanoma

Completed Phase 1 Results posted Last updated 9 August 2023
What this trial tests

Phase 1 trial testing Talimogene laherparepvec in Unresectable Stage IIIB-IV Malignant Melanoma in 18 participants. Completed in 12 January 2023.

Timeline
7 March 2017
Primary endpoint
3 August 2020
12 January 2023

Quick facts

Lead sponsorAmgen
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposeother
Enrollment18
Start date7 March 2017
Primary completion3 August 2020
Estimated completion12 January 2023
Sites9 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 99, any sex, with Unresectable Stage IIIB-IV Malignant Melanoma. 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.

Number of Participants Who Experienced One or More Dose Limiting Toxicities (DLTs) Primary · Day 1 to Day 35

DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4 Events were considered DLTs, if judged by the investigator to be related to study treatment: Grade 4 non-hematologic toxicity Grade 3 non-hematologic toxicity lasting \> 3 days despite optimal supportive care (grade 3 fatigue not a DLT) Grade 3 or higher non-hematologic laboratory value reported as an adverse event if: medical intervention is required, or abnormality leads to hospitalization, or abnormality persists for \> 1 week (Laboratory values that persist for \> 1 week but are deemed not clini

GroupValue95% CI
Talimogene Laherparepvec0
Durable Response Rate (DRR) Using Modified World Health Organization (WHO) Response Criteria Primary · Day 1 up to the maximum time on treatment or follow-up at primary data cutoff date (03 August 2020): 89.1 weeks of treatment and 37 months of follow-up

DRR using WHO response criteria was defined as the percentage of participants who experienced objective response (complete response \[CR\] or partial response \[PR\]) lasting continuously for ≥ 6 months that starting any time within 12 months of initiating treatment. CR: Complete disappearance of all index lesions, including any new tumors which might have appeared. PR: Achieving a 50% or greater reduction in the SPD of the perpendicular diameters of all index lesions at the time of assessment as compared to the sum of the products of the perpendicular diameters of all index lesions at basel

GroupValue95% CI
Talimogene Laherparepvec11.11.4 – 34.7
Overall Response Rate (ORR) Using Modified World Health Organization (WHO) Response Criteria Secondary · Day 1 to end of study, maximum time to end of study was 212.6 weeks

ORR was defined as the percentage of participants who experienced an objective response of CR or PR per modified WHO response criteria among the set of participants analyzed.

GroupValue95% CI
Talimogene Laherparepvec11.11.4 – 34.7
Time to Response (TTR) Using Modified World Health Organization (WHO) Response Criteria Secondary · Day 1 to end of study, maximum time to end of study was 212.6 weeks

TTR was defined as the time from the first treatment administration to the first incidence of a confirmed CR or PR according to modified WHO response criteria among the set of participants analyzed. TTR was estimated using Kaplan-Meier (KM) method.

GroupValue95% CI
Talimogene LaherparepvecNA8.08 – NA
Duration of Response (DOR) Using Using Modified World Health Organization (WHO) Response Criteria Secondary · Day 1 to end of study, maximum time to end of study was 212.6 weeks

DOR was defined as the time from the date of an initial response (CR or PR) to the earlier of progressive disease (PD) or death. Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment. PD: A \> 25% increase in the sum of the products of the perpendicular diameters of all index tumors since baseline, or the unequivocal appearance of a new tumor since the last response assessment time point. DOR was estimated using Kaplan-Meier (KM) method.

GroupValue95% CI
Talimogene LaherparepvecNA11.07 – NA
Progression Free Survival (PFS) Using Using Modified World Health Organization (WHO) Response Criteria Secondary · Day 1 to end of study, maximum time to end of study was 212.6 weeks

PFS was defined as the interval from the first dose to the earlier of PD per modified WHO response criteria or death from any cause; otherwise, PFS was censored at the last evaluable tumor assessment. PFS was estimated using Kaplan-Meier (KM) method.

GroupValue95% CI
Talimogene Laherparepvec3.072.56 – 5.78
Overall Survival (OS) Secondary · Day 1 to end of study, maximum time to end of study was 212.6 weeks

OS was defined as the interval from first dose to the event of death from any cause; otherwise, OS was censored at the date the participant was last known to be alive. OS was estimated using Kaplan-Meier (KM) method.

GroupValue95% CI
Talimogene LaherparepvecNA17.51 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Deaths: From enrollment to end of study, up to maximum of 212.6 weeks; SAE and non-serious AEs: Day 1 (post 1st dose) to 30 days after last dose. Median (min, max) duration of treatment overall was 23.14 (3.1, 201.6) weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Talimogene Laherparepvec
Serious: 6/18 (33%)
Deaths: 8/18

Serious adverse events (9 terms)

ReactionSystemTalimogene Laherparepvec
MalaiseGeneral disorders
Jaundice cholestaticHepatobiliary disorders
Enteritis infectiousInfections and infestations
EpiglottitisInfections and infestations
PneumoniaInfections and infestations
Forearm fractureInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders
Malignant melanomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
HaemorrhageVascular disorders
Other adverse events (49 terms — click to expand)

ReactionSystemTalimogene Laherparepvec
PyrexiaGeneral disorders
NasopharyngitisInfections and infestations
ConstipationGastrointestinal disorders
Gingival painGastrointestinal disorders
NauseaGastrointestinal disorders
ChillsGeneral disorders
FatigueGeneral disorders
MalaiseGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
Skin ulcerSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Injection site reactionGeneral disorders
Oedema peripheralGeneral disorders
PainGeneral disorders
Jaundice cholestaticHepatobiliary disorders
Seasonal allergyImmune system disorders
Bacterial infectionInfections and infestations
Subcutaneous abscessInfections and infestations
Upper respiratory tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
ArthritisMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
TenosynovitisMusculoskeletal and connective tissue disorders
SyncopeNervous system disorders
HaematuriaRenal and urinary disorders
PollakiuriaRenal and urinary disorders
Benign prostatic hyperplasiaReproductive system and breast disorders
CoughRespiratory, thoracic and mediastinal disorders
Laryngeal painRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Pharyngeal inflammationRespiratory, thoracic and mediastinal disorders
AcneSkin and subcutaneous tissue disorders
Alopecia areataSkin and subcutaneous tissue disorders

Most-reported serious reactions: Malaise, Jaundice cholestatic, Enteritis infectious, Epiglottitis, Pneumonia, Forearm fracture, Decreased appetite, Malignant melanoma.

Data from ClinicalTrials.gov NCT03064763 adverse events section.

Sponsor's own description

There are 2 fold of purposes for this study. 1 is to evaluate safety and tolerability and the other is to study the anti-tumor effects of talimogene laherparepvec in Japanese participants with unresectable stage IIIB-IV malignant melanoma.

Publications & conference data

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

  1. Targeted Therapy and Immunotherapy for Melanoma in Japan.
    Namikawa K, Yamazaki N. · · 2019 · cited 103× · PMID 30675668 · DOI 10.1007/s11864-019-0607-8
  2. 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
  3. 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
  4. Talimogene Laherparepvec (T-VEC): A Review of the Recent Advances in Cancer Therapy.
    Zhang T, Jou TH, Hsin J, Wang Z, et al · · 2023 · cited 50× · PMID 36769745 · DOI 10.3390/jcm12031098
  5. 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
  6. Beyond Immunotherapy: Seizing the Momentum of Oncolytic Viruses in the Ideal Platform of Skin Cancers.
    Ziogas DC, Martinos A, Petsiou DP, Anastasopoulou A, et al · · 2022 · cited 9× · PMID 35740539 · DOI 10.3390/cancers14122873
  7. A phase I study of the safety and efficacy of talimogene laherparepvec in Japanese patients with advanced melanoma.
    Yamazaki N, Isei T, Kiyohara Y, Koga H, et al · · 2022 · cited 8× · PMID 35656636 · DOI 10.1111/cas.15450
  8. Where Are We Now with Oncolytic Viruses in Melanoma and Nonmelanoma Skin Malignancies?
    Nassief G, Anaeme A, Moussa K, Chen D, et al · · 2024 · cited 2× · PMID 39065766 · DOI 10.3390/ph17070916

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