COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Single-arm Trial to Evaluate the Role of the Immune Response to Talimogene Laherparepvec in Unresected Melanoma (TVEC-325)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02366195
Recruitment Status : Completed
First Posted : February 19, 2015
Results First Posted : July 18, 2018
Last Update Posted : January 26, 2021
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
The study is a phase 2, multi centered, single arm study designed to evaluate the correlation between cluster of differentiation 8-positive (CD8+) cell density and objective response rate in adults with unresected stage IIIB to IVM1c melanoma. This study will also evaluate the safety and tolerability profile of talimogene laherparepvec.

Condition or disease Intervention/treatment Phase
Unresected Stage IIIb to IVM1c Melanoma Drug: Talimogene Laherparepvec Phase 2

Detailed Description:
The study will explore the hypothesis that intratumoral CD8+ cell density at baseline correlates with objective response rate in adults with unresected stage IIIB to IVMIc melanoma treated with talimogene laherparepvec.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 112 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Open-label, Single-arm Trial to Evaluate the Correlation Between Objective Response Rate and Baseline Intratumoral CD8+ Cell Density in Subjects With Unresected Stage IIIB to IVM1c Melanoma Treated With Talimogene Laherparepvec
Actual Study Start Date : April 7, 2015
Actual Primary Completion Date : June 26, 2017
Actual Study Completion Date : December 25, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Talimogene Laherparepvec
Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.
Drug: Talimogene Laherparepvec
The initial dose of talimogene laherparepvec is up to 4.0 mL of 10^6 PFU/mL. Subsequent doses of talimogene laherparepvec are up to 4.0 mL of 10^8 PFU/mL.
Other Name: IMLYGIC®




Primary Outcome Measures :
  1. Correlation Between Baseline Intratumoral CD8+ Cell Density and Objective Response Rate [ Time Frame: Intratumoral CD8+ cell density was assessed at Baseline. Response was assessed every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up was 59 weeks (range 3 - 116 weeks). ]

    A univariate logistic regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of objective response.

    Response was assessed according to the modified version of the World Health Organization (WHO) response criteria. Objective response rate (ORR) was defined as the percentage of participants with a complete response or partial response according to the modified WHO criteria.

    The unadjusted odds ratio of log2(baseline intratumoral CD8+ cell density) for objective response rate is reported.



Secondary Outcome Measures :
  1. Correlation Between Baseline Intratumoral CD8+ Cell Density and Durable Response Rate [ Time Frame: Intratumoral CD8+ cell density was assessed at Baseline. Response was assessed every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up was 59 weeks (range 3 - 116 weeks). ]

    A univariate logistic regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of durable response.

    Response was assessed according to the modified version of the World Health Organization (WHO) response criteria. Durable response rate (DRR) was defined as the percentage of participants with an objective response lasting continuously for 6 months and starting any time within 12 months of initiating therapy.

    The unadjusted odds ratio of log2(baseline intratumoral CD8+ cell density) for durable response rate is reported.


  2. Correlation Between Baseline Intratumoral CD8+ Cell Density and Duration of Response [ Time Frame: Intratumoral CD8+ cell density was assessed at Baseline. Response was assessed every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up was 59 weeks (range 3 - 116 weeks). ]

    A Cox proportional hazards regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of duration of response.

    Response was assessed according to the modified version of the World Health Organization (WHO) response criteria. Duration of response (DOR) is defined as the longest individual period from entering an objective response (CR/PR) to the first documented evidence of the participant no longer meeting the criteria for being in the response (i.e. an overall response of either stable disease [SD] as compared with baseline or progressive disease [PD]).

    The unadjusted hazard ratio of log2(baseline intratumoral CD8+ cell density) for duration of response is reported.


  3. Correlation Between Baseline Intratumoral CD8+ Cell Density and Changes in Tumor Burden [ Time Frame: Intratumoral CD8+ cell density was assessed at baseline. Disease burden was assessed every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up was 59 (range 3 - 116) weeks. ]

    Pearson's correlation coefficient (r) was estimated to assess the relationship between baseline log2(CD8+ cell density) and the maximum decrease in measurable tumor burden.

    Tumor burden is the sum of the products of the 2 largest perpendicular diameters (SPD) for all index lesions selected at baseline.

    The Pearson's correlation coefficient (r) of log2(baseline intratumoral CD8+ cell density) and the maximum decrease in tumor burden is reported.


  4. Correlation Between Change From Baseline Intratumoral CD8+ Cell Density and Objective Response Rate [ Time Frame: Intratumoral CD8+ cell density was assessed at Baseline and week 6. Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up was 59 weeks (range 3 - 116 weeks). ]

    A univariate logistic regression model was performed to evaluate change from baseline to week 6 in log2(CD8+ cell density) in uninjected tumors as a predictor of objective response.

    Response was assessed according to the modified version of the World Health Organization (WHO) response criteria. Objective response rate (ORR) was defined as the percentage of participants with a complete response or partial response according to the modified WHO criteria.

    The unadjusted odds ratio of log2(change from baseline intratumoral CD8+ cell density) for objective response rate is reported.


  5. Correlation Between Change From Baseline in Intratumoral CD8+ Cell Density and Durable Response Rate [ Time Frame: Intratumoral CD8+ cell density was assessed at Baseline and week 6. Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up was 59 weeks (range 3 - 116 weeks). ]

    A univariate logistic regression model was performed to evaluate change from baseline to week 6 in log2(CD8+ cell density) in uninjected lesions as a predictor of durable response.

    Response was assessed according to the modified version of the World Health Organization (WHO) response criteria. Durable response rate (DRR) was defined as the percentage of participants with an objective response lasting continuously for 6 months and starting any time within 12 months of initiating therapy.

    The unadjusted odds ratio of log2(change from baseline in intratumoral CD8+ cell density) for durable response rate is reported.


  6. Correlation Between Change From Baseline in Intratumoral CD8+ Cell Density and Duration of Response [ Time Frame: Intratumoral CD8+ cell density was assessed at Baseline and week 6. Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up was 59 weeks (range 3 - 116 weeks). ]

    A Cox proportional hazards regression model was performed to evaluate change from baseline in log2(CD8+ cell density) as a predictor of duration of response.

    Response was assessed according to the modified version of the World Health Organization (WHO) response criteria. Duration of response (DOR) is defined as the longest individual period from entering an objective response (CR/PR) to the first documented evidence of the participant no longer meeting the criteria for being in the response (i.e. an overall response of either stable disease [SD] as compared with baseline or progressive disease [PD]).

    The unadjusted hazard ratio of log2(change from baseline intratumoral CD8+ cell density) for duration of response is reported.


  7. Correlation Between Change From Baseline in Intratumoral CD8+ Cell Density and Changes in Tumor Burden [ Time Frame: Intratumoral CD8+ cell density was assessed at baseline and week 6. Tumor burden was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up was 59 (range 3 - 116) weeks. ]

    Pearson's correlation coefficient (r) was estimated to assess the relationship between change from baseline in log2(CD8+ cell density) in uninjected lesions and the maximum decrease in measurable tumor burden.

    Tumor burden is the sum of the products of the 2 largest perpendicular diameters (SPD) for all index lesions selected at baseline.

    The Pearson's correlation coefficient (r) of log2(change from baseline intratumoral CD8+ cell density) and the maximum decrease in tumor burden is reported.


  8. Objective Response Rate [ Time Frame: Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at the time of the data cut-off date (26 June 2017) was 59 weeks (range 3 to 116 weeks). ]

    Objective Response rate is defined as the percentage of participants with either a complete response (CR) or partial response (PR) based on Modified WHO Response Criteria.

    CR: Complete disappearance of all index lesions, all non-index lesions, and any new tumors which might have appeared. Any residual cutaneous or subcutaneous index lesions must be documented by representative biopsy to not contain viable tumor.

    PR: Disappearance of all index lesions with persistence of one or more non-index tumor(s), or, 50% or greater reduction in the SPD of all index lesions as compared to baseline, and disappearance or persistence of non-index lesions.


  9. Duration of Response [ Time Frame: Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at the time of the data cut-off date (26 June 2017) was 59 weeks (range 3 to 116 weeks). ]

    Duration of response (DOR) was defined as the longest individual period from entering an objective response (CR/PR) to the first documented evidence of the participant no longer meeting the criteria for objective response (i.e. an overall response of either stable disease [SD] as compared with baseline or progressive disease [PD]).

    SD: Neither sufficient tumor shrinkage of index lesion to qualify for response (PR or CR) nor sufficient tumor increase of index lesion to qualify for PD, with no increase in size of non-index lesions.

    PD: A > 25% increase in the sum of the SPD of all index tumors since baseline, or the unequivocal appearance of a new tumor since the last response assessment time point, or unequivocal progression of one or more non-index lesions.

    Participants last reported to be either a CR or PR were censored at that time point.


  10. Time to Treatment Failure [ Time Frame: From first dose of study drug until the data cut-off date of 26 June 2017; median time on follow-up was 59 weeks (range 3 to 116 weeks). ]
    Time to treatment failure (TTF) was calculated from first dosing until one or more of the following: (1) clinically relevant disease progression (PDr); (2) death from any cause; (3) non clinically relevant disease progression (PDn) associated with a requirement for alternative therapy as the reason for ending treatment or start of new anti-cancer therapy. Participants with no event were censored at their last evaluable tumor assessment.

  11. Durable Response Rate [ Time Frame: Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at the time of the data cut-off date (26 June 2017) was 59 weeks (range 3 to 116 weeks). ]
    Durable response rate (DRR) was defined as the percentage of participants with an objective response (CR or PR) based on modified WHO response criteria lasting continuously for 6 months and starting any time within 12 months of initiating therapy.

  12. Overall Survival [ Time Frame: From first dose of study drug until the data cut-off date of 26 June 2017; median time on follow-up was 59 weeks (range 3 to 116 weeks). ]

    Overall survival (OS) was defined as the time from the date of first dose to the date of death from any cause.

    OS time was censored at the last date the participant was known to be alive when the confirmation of death is absent or unknown.


  13. Change From Baseline in Tumor Burden [ Time Frame: Baseline and cycle 6 day 1, cycle 12 day 1, cycle 18 day 1, and cycle 24 day 1. The first cycles was 21 days and all subsequent cycles were 14 days. ]

    Tumor burden is the sum of the products of the 2 largest perpendicular diameters (SPD) for all index lesions selected at baseline.

    Change from baseline in tumor burden was assessed in participants with an objective response.


  14. Number of Participants With Adverse Events [ Time Frame: From first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25 (range 0.1 - 84) weeks. ]
    The severity of each adverse event (AE) was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 grading scale, where Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE Treatment-related adverse events (TRAE) were those assessed by the investigator as possibly related to talimogene laherparepvec.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provided informed consent prior to initiation of any study-specific activities/procedures
  2. Subject with stage IIIB to IVM1c melanoma for whom surgery is not recommended
  3. Candidate for intralesional therapy
  4. Measurable disease with greatest diameter ≥ 10 mm
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  6. Adequate organ function

Other Inclusion Criteria May Apply

Exclusion Criteria:

  1. Clinically active cerebral metastases.
  2. Bone metastases
  3. Primary ocular or mucosal melanoma
  4. Active herpetic skin lesions or prior complications of herpes simplex virus type 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis)
  5. Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use
  6. Female subject is pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of talimogene laherparepvec
  7. Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception

Other Exclusion Criteria May Apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02366195


Locations
Layout table for location information
United States, Utah
Research Site
Salt Lake City, Utah, United States, 84112
Austria
Research Site
Salzburg, Austria, 5020
Research Site
Wien, Austria, 1090
Belgium
Research Site
Bruxelles, Belgium, 1000
Research Site
Bruxelles, Belgium, 1200
Research Site
Liege, Belgium, 4000
France
Research Site
Boulogne Billancourt, France, 92100
Research Site
Marseille cedex 05, France, 13385
Research Site
Nantes Cedex 1, France, 44093
Research Site
Paris, France, 75010
Research Site
Poitiers Cedex, France, 86021
Germany
Research Site
Essen, Germany, 45147
Research Site
Frankfurt am Main, Germany, 60590
Research Site
Hannover, Germany, 30625
Research Site
Heidelberg, Germany, 69120
Greece
Research Site
Athens, Greece, 11527
Research Site
Athens, Greece, 18547
Research Site
Heraklion - Crete, Greece, 71110
Research Site
Patra, Greece, 26504
Research Site
Thessaloniki, Greece, 54622
Hungary
Research Site
Budapest, Hungary, 1085
Research Site
Budapest, Hungary, 1122
Research Site
Debrecen, Hungary, 4032
Research Site
Pecs, Hungary, 7632
Research Site
Szeged, Hungary, 6720
Italy
Research Site
Bergamo, Italy, 24127
Research Site
Milano, Italy, 20141
Research Site
Siena, Italy, 53100
Netherlands
Research Site
Amsterdam, Netherlands, 1081 HV
Research Site
Groningen, Netherlands, 9713 GZ
Poland
Research Site
Konin, Poland, 62-500
Research Site
Warszawa, Poland, 02-781
Russian Federation
Research Site
Moscow, Russian Federation, 115478
Research Site
Saint-Petersburg, Russian Federation, 197758
Spain
Research Site
Badalona, Cataluña, Spain, 08916
Research Site
Barcelona, Cataluña, Spain, 08036
Research Site
Valencia, Comunidad Valenciana, Spain, 46014
Research Site
San Sebastian, País Vasco, Spain, 20014
Research Site
Madrid, Spain, 28009
Research Site
Madrid, Spain, 28041
United Kingdom
Research Site
London, United Kingdom, SE1 9RT
Research Site
Wirral, United Kingdom, CH63 4JY
Sponsors and Collaborators
Amgen
Investigators
Layout table for investigator information
Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] September 21, 2015
Statistical Analysis Plan  [PDF] August 20, 2014

Additional Information:
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02366195    
Other Study ID Numbers: 20120325
2013-005552-15 ( EudraCT Number )
First Posted: February 19, 2015    Key Record Dates
Results First Posted: July 18, 2018
Last Update Posted: January 26, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing
Keywords provided by Amgen:
T-VEC
CD8+ cell density
objective response rate
unresected
Melanoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Talimogene laherparepvec
Antineoplastic Agents, Immunological
Antineoplastic Agents