Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Talimogene laherparepvec

Antineoplastic Agents, Immunological

Up to 4ml of talimogene laherparepvec per cycle visit

Talimogene Laherparepvec

Expanded access of Talimogene Laherparepvec for subjects with unresected, stage IIIb to IVM1c Melanoma.

Expanded access of Talimogene Laherparepvec for subjects with unresected, stage IIIb to IVM1c Melanoma that may not meet the eligibility criteria to enroll in another ongoing Talimogene Laherparepvec study or do not have access to enroll in an ongoing Talimogene Laherparepvec study.

Expanded Access Protocol of Talimogene Laherparepvec for Subjects With Unresected, Stage lllB to IVM1c Melanoma

A Phase 3b, Multicenter, Open-label, Single-arm, Expanded Access Protocol of Talimogene Laherparepvec for the Treatment of Subjects With Unresected, Stage lllB to IVM1c Melanoma

Amgen

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.

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.

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.

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.

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

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

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care, unable to carry out any work activities. Up and about \> 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair \> 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Primary completion

Final analysis

CD8+ cell density was assessed from tumor biopsy samples using CD8-specific immunohistochemistry.

Participants with non-missing data. Baseline data is available for 91 participants who had data available for analysis at the time of primary completion (26 June 2017). Baseline data is also presented for 93 participants who had data available at final analysis (25 December 2020).

Log2(Intratumoral Cluster of Differentiation 8-positive (CD8+) Cell Density)

Participants who received at least 1 dose of talimogene laherparepvec.

Study Director

Participants who received at least 1 dose of talimogene laherparepvec with non-missing baseline CD8+ cell density data. Data is available for 91 participants who had data available for analysis at the time of primary completion (26 June 2017).

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

Participants who received at least 1 dose of talimogene laherparepvec with non-missing baseline CD8+ cell density data. Data is available for 91 participants who had data available for analysis at the time of primary completion (26 June 2017). Data is also presented for 93 participants who had data available at final analysis (25 December 2020).

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

Participants who received at least 1 dose of talimogene laherparepvec with an objective response at the time of primary completion or final analysis, and with baseline CD8+ cell density data.

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

Participants who received at least 1 dose of talimogene laherparepvec with available tumor burden data at primary completion or final analysis, and baseline CD8+ cell density data.

Correlation Between Baseline Intratumoral CD8+ Cell Density and Changes in Tumor Burden

Participants who received at least 1 dose of talimogene laherparepvec with baseline and week 6 CD8+ cell density data for uninjected lesions. Data is available for 59 participants who had data available for analysis at the time of primary completion (26 June 2017). Data is also presented for 63 participants who had data available at final analysis (25 December 2020).

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

Participants who received at least 1 dose of talimogene laherparepvec with baseline and week 6 CD8+ cell density data in uninjected lesions. Data is available for 59 participants who had data available for analysis at the time of primary completion (26 June 2017). Data is also presented for 63 participants who had data available at final analysis (25 December 2020).

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

Participants who received at least 1 dose of talimogene laherparepvec with an objective response at either primary completion or final analysis, and with baseline and week 6 CD8+ cell density data for uninjected lesions.

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

Participants who received at least 1 dose of talimogene laherparepvec with available tumor burden data at primary completion or final analysis, and baseline and week 6 CD8+ cell density data for uninjected lesions.

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

All participants who received at least 1 dose of talimogene laherparepvec.

Objective Response Rate

Participants who received at least 1 dose of talimogene laherparepvec with an objective response at either primary completion (26 June 2017) or final analysis (25 December 2020).

Duration of Response

Time to Treatment Failure

Durable Response Rate

Overall Survival

Baseline

Change from baseline at Cycle 6 day 1

Change from baseline at Cycle 12 day 1

Change from baseline at Cycle 18 day 1

Change from baseline at Cycle 24 day 1

Change from baseline at Cycle 30 day 1

Change from baseline at Cycle 36 day 1

Change from baseline at Cycle 42 day 1

Change from baseline at Cycle 48 day 1

Change from baseline at Cycle 54 day 1

Change from baseline at Cycle 60 day 1

Change from baseline at Cycle 66 day 1

Change from baseline at Cycle 72 day 1

Change from baseline at Cycle 78 day 1

Change from baseline at Cycle 84 day 1

Change from baseline at Cycle 90 day 1

Change from baseline at Cycle 96 day 1

Change from baseline at Cycle 102 day 1

Change from baseline at Cycle 108 day 1

Change from baseline at Cycle 114 day 1

Change from baseline at Cycle 120 day 1

Participants who received at least 1 dose of talimogene laherparepvec with an objective response (CR or PR)

Change From Baseline in Tumor Burden

Any adverse event

Adverse events ≥ grade 3

Adverse events ≥ grade 4

Serious adverse events

AE leading to discontinuation of study drug

Fatal adverse events

Treatment-related adverse events

Treatment-related adverse events ≥ grade 3

Treatment-related adverse events ≥ grade 4

Treatment-related serious adverse events

TRAE leading to discontinuation of study drug

Treatment-related fatal adverse events

Number of Participants With Adverse Events

Overall Study

Open label single arm study. The initial dose of talimogene laherparepvec is up to 4.0 mL of 106 PFU/mL. Subsequent doses of talimogene laherparepvec are up to 4.0 mL of 108 PFU/mL.

The study is a phase 3b, multicenter, open-label, single-arm study designed to provide expanded access of Talimogene Laherparepvec for the treatment of subjects with unresected stage IIIB to IVM1c melanoma. The study will also evaluate the safety and tolerability of Talimogene Laherparepvec.

This is a phase 3b, multicenter, open-label, single-arm, expanded access study of talimogene laherparepvec for the treatment of subjects with unresected stage IIIB to IVM1c melanoma in select European countries. Subjects with unresected stage lllB-IVM1c melanoma who are not eligible for or cannot access ongoing talimogene laherparepvec clinical trials and who meet the eligibility criteria outlined will be considered for participation in this protocol. Eligible subjects will be treated with talimogene laherparepvec until the subject has achieved a complete response, all injectable tumors have disappeared, clinically relevant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of therapy, intolerance of protocol treatment, or until talimogene laherparepvec receives marketing authorization approval in Europe for the treatment of melanoma, whichever occurs first. Subjects will be followed for safety approximately 30 (+7) days after the end of treatment. Thereafter, subjects who provide consent will be followed under an ongoing separate registry protocol for the long-term survival follow-up of subjects treated with talimogene laherparepvec in clinical trials. The registry protocol will also monitor for late and long-term adverse events thought to be potentially related to talimogene laherparepvec.

Expanded Access Study of Talimogene Laherparepvec for Treatment of Subjects With Unresected Stage IIIB-IVM1c Melanoma

A Phase 3b, Multicenter, Open-label, Single-arm, Expanded Access Protocol of Talimogene Laherparepvec for the Treatment of Subjects in Europe With Unresected Stage IIIB to IVM1c Melanoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Expanded Access Protocol of Talimogene Laherparepvec for Subjects With Unresected, Stage lllB to IVM1c Melanoma	NCT02147951	Unresected Stag...	Talimogene Lahe...	18 Years - 95 Years	Amgen
Single-arm Trial to Evaluate the Role of the Immune Response to Talimogene Laherparepvec in Unresected Melanoma	NCT02366195	Unresected Stag...	Talimogene Lahe...	18 Years -	Amgen
Expanded Access Study of Talimogene Laherparepvec for Treatment of Subjects With Unresected Stage IIIB-IVM1c Melanoma	NCT02297529	Unresected Stag...	Talimogene Lahe...	18 Years - 95 Years	Amgen
Expanded Access Study of Talimogene Laherparepvec for Treatment of Subjects With Unresected Stage IIIB-IVM1c Melanoma	NCT02297529	Unresected Stag...	Talimogene Lahe...	18 Years - 95 Years	Amgen
Expanded Access Study of Talimogene Laherparepvec for Treatment of Subjects With Unresected Stage IIIB-IVM1c Melanoma	NCT02297529	Unresected Stag...	Talimogene Lahe...	18 Years - 95 Years	Amgen
Single-arm Trial to Evaluate the Role of the Immune Response to Talimogene Laherparepvec in Unresected Melanoma	NCT02366195	Unresected Stag...	Talimogene Lahe...	18 Years -	Amgen

Spots Global Cancer Trial Database for unresected stage iiib to ivm1c melanoma