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Completed

NCT Number: NCT02366195

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

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.

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Key information

Conditions

Unresected Stage IIIb to IVM1c Melanoma Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site, Salzburg, Austria

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Other Inclusion Criteria May Apply

Exclusion criteria

  • Clinically active cerebral metastases.
  • Bone metastases
  • Primary ocular or mucosal melanoma
  • Active herpetic skin lesions or prior complications of herpes simplex virus type 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis)
  • Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use
  • 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
  • Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception

Other Exclusion Criteria May Apply

Treatment and study plan

Talimogene Laherparepvec

Drug

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 names: IMLYGIC®

Primary outcomes

  1. Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Objective Response Rate

    Time frame: Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at primary completion = 59 weeks (min 3 to max 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 (CR) or partial response (PR) according to the modified WHO criteria.

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

Secondary outcomes

  1. Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Durable Response Rate

    Time frame: Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6)

    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.

    Primary completion is defined as PC and final analysis is defined as FA.

  2. Hazards Ratio of Baseline Intratumoral CD8+ Cell Density and Duration of Response

    Time frame: Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 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: Baseline; Tumor burden: First dose of study drug until primary completion date (26 June 2017) or end of follow-up; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 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.

    Primary completion is defined as PC and final analysis is defined as FA.

  4. Odds Ratio of Change From Baseline Intratumoral CD8+ Cell Density and Objective Response Rate

    Time frame: CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 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.

    Intratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.

  5. Odds Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Durable Response Rate

    Time frame: CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 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.

    Intratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.

  6. Hazard Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Duration of Response

    Time frame: CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 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.

    Intratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.

  7. Correlation Between Change From Baseline in Intratumoral CD8+ Cell Density and Changes in Tumor Burden

    Time frame: CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 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.

    Intratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.

  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 time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 weeks)

    Objective Response rate is defined as the percentage of participants with either a CR or 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 2 largest perpendicular diameters (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 time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 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 primary completion date of 26 June 2017, or end of follow-up; median time on follow-up at primary completion was 59 weeks (3 to 116 weeks); final analysis was 108 weeks (2.7 to 245.6 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 time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 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 primary completion date of 26 June 2017, or end of follow-up; median time on follow-up at primary completion was 59 weeks (3 to 116 weeks); final analysis was 108 weeks (2.7 to 245.6 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 Day 1 of cycle 6, 12 , 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, and 120. The first cycle 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 25.143 weeks (range 0.14 to 241.43 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.

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Official study 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

Acronym: TVEC-325

Important dates

Study start
2015
Primary completion
2017
Study completion
2020
First posted
Feb 19, 2015
Registry last updated
Nov 30, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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