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

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 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 (CR), all injectable tumors had disappeared, clinically relevant (resulting in clinical deterioration or requiring change of therapy) disease progression per modified World Health Organization (WHO) response criteria beyond 6 months of therapy, or intolerance of study treatment, whichever occurred first.

Talimogene laherparepvec will be administered by intralesion injection at an initial dose of up to 4.0 mL of 10\^6 PFU/mL. The second and subsequent doses will will be up to 4.0 mL 10\^8 PFU/mL. The second dose should be administered 21 days from the initial dose. All subsequent doses should be given every 14 days.

The primary objective was to estimate the proportion of participants with detectable talimogene laherparepvec deoxyribonucleic acid (DNA) in the blood and urine at any time after administration of talimogene laherparepvec within the first 3 cycles.

Single-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec

A Phase 2, Multicenter, Single-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec in Subjects With Unresected, Stage IIIB to IVM1c Melanoma

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in blood or urine at any time during cycles 1 to 3 is reported. The first cycle was 21 days in length, and subsequent cycles were 14 days in length.

A participant was defined as having cleared talimogene laherparepvec if a negative blood sample was obtained following a prior positive test and if there were no subsequent positive tests.

A participant was defined as having cleared talimogene laherparepvec if a negative urine sample was obtained following a prior positive test and if there were no subsequent positive tests.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the exterior of the occlusive dressing with detectable talimogene laherparepvec DNA at any time during cycles 1 to 3 is reported.

If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of swab samples from the exterior of the occlusive dressing with detectable talimogene laherparepvec virus at any time during cycles 1 to 3 is reported.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA on the exterior of the occlusive dressing at any time during cycles 1 to 3 is reported.

If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus on the exterior of the occlusive dressing at any time during cycles 1 to 3 is reported.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the surface of injected lesions with detectable talimogene laherparepvec DNA at any time during cycles 1 to 3 is reported.

If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of samples taken from the surface of injected lesions with detectable talimogene laherparepvec virus at any time during cycles 1 to 3 is reported.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA swabs taken from the surface of injected lesions at any time during cycles 1 to 3 is reported.

If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus on swabs taken from the surface of injected lesions at any time during cycles 1 to 3 is reported.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from oral mucosa with detectable talimogene laherparepvec DNA at any time during treatment is reported.

If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of samples taken from oral mucosa with detectable talimogene laherparepvec virus at any time during treatment is reported.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA on swabs taken from oral mucosa at any time during treatment is reported.

If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus in swabs taken from oral mucosa at any time during treatment is reported.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the anogenital area with detectable talimogene laherparepvec DNA at any time during treatment is reported.

If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of samples with detectable talimogene laherparepvec virus in swabs taken from the anogenital area at any time during treatment is reported.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in swabs from the anogenital area at any time during treatment is reported.

If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus in swabs taken from the anogenital area at any time during treatment is reported.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from oral mucosa with detectable talimogene laherparepvec DNA after the end of treatment is reported.

If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in swabs taken from oral mucosa after the end of treatment is reported.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the anogenital area with detectable talimogene laherparepvec DNA after the end of treatment is reported.

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in swabs from the anogenital area after the end of treatment is reported.

Any lesion such as a cold sore or vesicle thought to be herpetic in origin was evaluated by the investigator and swabbed if HSV infection was suspected. Quantitative PCR was performed on the swab sample to evaluate whether talimogene laherparepvec DNA was detectable in the sample.

Response was assessed according to modified World Health Organization (WHO) criteria using both clinical (cutaneous, subcutaneous, or nodal tumor measurement by caliper) and radiological imaging (computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound of the chest, abdomen, and pelvis and all other sites of disease).

Complete response: disappearance of all index and non-index lesions.

Partial Response: ≥ 50% reduction in size of all index lesions and any new measurable lesions.

Stable disease: Neither sufficient tumor shrinkage of index lesion to qualify for response nor sufficient tumor increase of index lesion to qualify for progressive disease, assessed a minimum interval of 77 days from the first dose of study drug.

Progressive Disease: ≥ 25% increase in size of index lesions or appearance of one or more non-index lesions.

Response was assessed according to modified World Health Organization (WHO) criteria using both clinical (cutaneous, subcutaneous, or nodal tumor measurement by caliper) and radiological imaging (computed tomography, magnetic resonance imaging or ultrasound of the chest, abdomen, and pelvis and all other sites of disease). Objective response rate is defined as the percentage of participants with either a complete response or partial response. Subsequent confirmation was not required.

Complete response: disappearance of all index and non-index lesions.

Partial Response: ≥ 50% reduction in size of all index lesions and any new measurable lesions.

Time to response was defined as the interval from the first dose of talimogene laherparepvec to the first event of complete response or partial response per modified WHO criteria; participants who did not respond were censored at the last evaluable tumor assessment.

Duration of response (DOR) was calculated only for those participants with an objective response and defined as the longest interval from an initial objective response (complete response or partial response) to disease progression per the modified WHO criteria or death, whichever occurred earlier; otherwise, DOR was censored at the last evaluable tumor assessment for participants who did not die or progress.

Response was assessed according to modified World Health Organization (WHO) criteria using both clinical (cutaneous, subcutaneous, or nodal tumor measurement by caliper) and radiological imaging (computed tomography, magnetic resonance imaging or ultrasound of the chest, abdomen, and pelvis and all other sites of disease). Durable response rate is defined as the percentage of participants with a complete response or partial response maintained continuously for at least 6 months (183 days).

Complete response: disappearance of all index and non-index lesions.

Partial Response:≥ 50% reduction in size of all index lesions and any new measurable lesions.

Overall Survival (OS) was defined as the interval from first dose of talimogene laherparepvec to death from any cause; participants still alive were censored at the last known alive date.

The Common Terminology Criteria for Adverse Events version 3.0 was used to grade severity of adverse events, based on the following general guideline: 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. A serious adverse event was defined as an adverse event that meets at least 1 of the following serious criteria:

* fatal
* life threatening
* requires in-patient hospitalization or prolongation of existing hospitalization
* results in persistent or significant disability/incapacity
* congenital anomaly/birth defect
* other medically important serious event

Treatment-related adverse events (TRAEs) are defined as adverse events possibly caused by talimogene laherparepvec, as assessed by the investigator.

Amgen

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

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 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter.

Talimogene Laherparepvec

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Scale to assess a patient's disease status.

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

Eastern Cooperative Oncology Group (ECOG) Performance

HSV-1 status at baseline was determined by HSV-1 iimmunoglobulin G (IgG).

Herpes Simplex Virus Type 1 (HSV-1) Status

Safety analysis set (all participants who received at least 1 dose of talimogene laherparepvec)

Study Director

Blood

Urine

Participants who were seronegative at baseline for HSV-1.

Talimogene Laherparepvec: HSV-1 Negative

Participants who were seropositive at baseline for HSV-1.

Talimogene Laherparepvec: HSV-1 Positive

Participants who were enrolled, received at least 1 dose of talimogene laherparepvec, and had at least 1 postdose blood/urine sample collected.

Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) During the First Three Cycles

Cycle 1

Cycle 2

Cycle 3

Participants must have received at least 1 dose of talimogene laherparepvec, had at least 2 post-dose blood samples collected within the same dosing cycle with at least 1 positive talimogene laherparepvec DNA sample and at least 1 subsequent sample at any time during the cycle.

Percentage of Participants With Clearance of Talimogene Laherparepvec DNA From Blood

Participants received at least 1 dose of talimogene laherparepvec, had at least 2 post-dose urine samples collected within the same dosing cycle with at least 1 positive talimogene laherparepvec DNA sample and at least 1 subsequent sample at any time during the cycle.

Percentage of Participants With Clearance of Talimogene Laherparepvec DNA From Urine

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab collected from the exterior of the occlusive dressing.

Percentage of Samples With Detectable Talimogene Laherparepvec DNA on the Exterior of the Occlusive Dressing During the First Three Cycles

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab collected from the exterior of the occlusive dressing with a detectable qPCR result.

Percentage of Samples With Detectable Talimogene Laherparepvec Virus on the Exterior of the Occlusive Dressing During the First Three Cycles

Percentage of Participants With Detectable Talimogene Laherparepvec DNA on the Exterior of the Occlusive Dressing During the First Three Cycles

Percentage of Participants With Detectable Talimogene Laherparepvec Virus on the Exterior of the Occlusive Dressing During the First Three Cycles

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one injected lesion swab collected.

Percentage of Samples From the Surface of Injected Lesions With Detectable Talimogene Laherparepvec DNA During the First Three Cycles

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one injected lesion swab collected with a positive qPCR result.

Percentage of Samples From the Surface of Injected Lesions With Detectable Talimogene Laherparepvec Virus During the First Three Cycles

Percentage of Participants With Detectable Talimogene Laherparepvec DNA on the Surface of Injected Lesions During the First Three Cycles

Percentage of Participants With Detectable Talimogene Laherparepvec Virus on the Surface of Injected Lesions During the First Three Cycles

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one oral mucosa swab collected during treatment.

Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec DNA During Treatment

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one oral mucosa swab collected during treatment with a positive qPCR result.

Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec Virus During Treatment

Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Oral Mucosa During Treatment

Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Oral Mucosa During Treatment

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab from the anogenital area collected during treatment.

Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec DNA During Treatment

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab from the anogenital area collected during treatment with a positive qPCR result.

Percentage of Samples With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area During Treatment

Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Swabs From the Anogenital Area During Treatment

Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area During Treatment

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one oral mucosa swab collected after the end of treatment.

Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec DNA After the End of Treatment

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one oral mucosa swab collected after the end of treatment with a positive qPCR result.

Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec Virus After the End of Treatment

Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Oral Mucosa After the End of Treatment

Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Oral Mucosa After the End of Treatment

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab from the anogenital area collected after end of treatment.

Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec DNA After the End of Treatment

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab from the anogenital area collected after the end of treatment with a positive qPCR result.

Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec Virus After the End of Treatment

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab from the anogenital area collected after the end of treatment.

Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Swabs From the Anogenital Area After the End of Treatment

Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area After the End of Treatment

Participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab sample collected from lesions suspected to be herpetic in origin during the study.

Number of Samples With Detectable Talimogene Laherparepvec in Lesions Suspected to be Herpetic in Origin

Complete Response

Partial Response

Stable Disease

Progressive Disease

Unevaluable

Not Done

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

Best Overall Response

Objective Response Rate

Time to Response

All participants who received at least 1 dose of talimogene laherparepvec and had an objective response.

Spots Global Cancer Trial Database for Single-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

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