Trial Outcomes & Findings for Single-arm Trial to Evaluate the Role of the Immune Response to Talimogene Laherparepvec in Unresected Melanoma (NCT NCT02366195)
NCT ID: NCT02366195
Last Updated: 2021-11-30
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
112 participants
Primary outcome timeframe
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)
Results posted on
2021-11-30
Participant Flow
This study was conducted at 36 centers across 12 countries in Europe from 07 April 2015 to 25 December 2020.
Participant milestones
| Measure |
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.
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|---|---|
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Overall Study
STARTED
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112
|
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Overall Study
Received Study Drug
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111
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Overall Study
COMPLETED
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58
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Overall Study
NOT COMPLETED
|
54
|
Reasons for withdrawal
| Measure |
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.
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|---|---|
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Overall Study
Protocol-specified criteria
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3
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Overall Study
Withdrawal by Subject
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9
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Overall Study
Lost to Follow-up
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1
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Overall Study
Death
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41
|
Baseline Characteristics
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).
Baseline characteristics by cohort
| Measure |
Talimogene Laherparepvec
n=111 Participants
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.
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|---|---|
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Age, Continuous
|
65.7 years
STANDARD_DEVIATION 15.1 • n=111 Participants
|
|
Sex: Female, Male
Female
|
62 Participants
n=111 Participants
|
|
Sex: Female, Male
Male
|
49 Participants
n=111 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
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1 Participants
n=111 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
110 Participants
n=111 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=111 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
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0 Participants
n=111 Participants
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|
Race/Ethnicity, Customized
Asian
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0 Participants
n=111 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=111 Participants
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Race/Ethnicity, Customized
Multiple
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0 Participants
n=111 Participants
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|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
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0 Participants
n=111 Participants
|
|
Race/Ethnicity, Customized
White
|
111 Participants
n=111 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=111 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0 (Fully active, no restrictions)
|
87 Participants
n=111 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1 (Restricted but ambulatory)
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24 Participants
n=111 Participants
|
|
Log2(Intratumoral Cluster of Differentiation 8-positive (CD8+) Cell Density)
Primary completion
|
8.041 Log2 CD8+ cells/mm²
STANDARD_DEVIATION 1.903 • n=91 Participants • 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).
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|
Log2(Intratumoral Cluster of Differentiation 8-positive (CD8+) Cell Density)
Final analysis
|
8.109 Log2 CD8+ cells/mm²
STANDARD_DEVIATION 1.940 • n=93 Participants • 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).
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PRIMARY outcome
Timeframe: 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)Population: 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).
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=91 Participants
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.
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|---|---|
|
Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Objective Response Rate
|
1.11 ratio
Interval 0.87 to 1.42
|
SECONDARY outcome
Timeframe: 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)Population: 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).
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=93 Participants
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.
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|---|---|
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Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Durable Response Rate
Primary completion
|
1.40 ratio
Interval 0.99 to 1.97
|
|
Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Durable Response Rate
Final analysis
|
1.18 ratio
Interval 0.91 to 1.53
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SECONDARY outcome
Timeframe: 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)Population: 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.
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=29 Participants
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.
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|---|---|
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Hazards Ratio of Baseline Intratumoral CD8+ Cell Density and Duration of Response
Primary completion
|
0.74 ratio
Interval 0.39 to 1.37
|
|
Hazards Ratio of Baseline Intratumoral CD8+ Cell Density and Duration of Response
Final analysis
|
0.91 ratio
Interval 0.63 to 1.3
|
SECONDARY outcome
Timeframe: 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)Population: 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.
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=85 Participants
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.
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|---|---|
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Correlation Between Baseline Intratumoral CD8+ Cell Density and Changes in Tumor Burden
Primary completion
|
0.03 Pearson's correlation coefficient
Interval -0.19 to 0.24
|
|
Correlation Between Baseline Intratumoral CD8+ Cell Density and Changes in Tumor Burden
Final analysis
|
0.01 Pearson's correlation coefficient
Interval -0.2 to 0.23
|
SECONDARY outcome
Timeframe: 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)Population: 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).
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=63 Participants
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.
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|---|---|
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Odds Ratio of Change From Baseline Intratumoral CD8+ Cell Density and Objective Response Rate
Primary completion
|
0.94 ratio
Interval 0.72 to 1.24
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|
Odds Ratio of Change From Baseline Intratumoral CD8+ Cell Density and Objective Response Rate
Final analysis
|
0.98 ratio
Interval 0.76 to 1.27
|
SECONDARY outcome
Timeframe: 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)Population: 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).
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=63 Participants
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.
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|---|---|
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Odds Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Durable Response Rate
Primary completion
|
0.99 ratio
Interval 0.69 to 1.44
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|
Odds Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Durable Response Rate
Final analysis
|
0.93 ratio
Interval 0.68 to 1.25
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SECONDARY outcome
Timeframe: 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)Population: 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.
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=18 Participants
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.
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|---|---|
|
Hazard Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Duration of Response
Primary completion
|
1.28 ratio
Interval 0.47 to 3.47
|
|
Hazard Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Duration of Response
Final analysis
|
1.12 ratio
Interval 0.74 to 1.69
|
SECONDARY outcome
Timeframe: 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)Population: 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.
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=60 Participants
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.
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|---|---|
|
Correlation Between Change From Baseline in Intratumoral CD8+ Cell Density and Changes in Tumor Burden
Primary completion
|
-0.18 Pearson's correlation coefficient
Interval -0.42 to 0.09
|
|
Correlation Between Change From Baseline in Intratumoral CD8+ Cell Density and Changes in Tumor Burden
Final analysis
|
-0.19 Pearson's correlation coefficient
Interval -0.43 to 0.06
|
SECONDARY outcome
Timeframe: 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)Population: All participants who received at least 1 dose of talimogene laherparepvec.
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=111 Participants
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.
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|---|---|
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Objective Response Rate
Primary completion
|
27.0 percentage of participants
Interval 19.0 to 36.3
|
|
Objective Response Rate
Final analysis
|
28.8 percentage of participants
Interval 20.6 to 38.2
|
SECONDARY outcome
Timeframe: 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)Population: 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 (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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=32 Participants
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.
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|---|---|
|
Duration of Response
Primary completion
|
NA months
Interval 11.5 to
Not reached at time of analysis as most participants were still in response.
|
|
Duration of Response
Final analysis
|
NA months
Interval 14.1 to
Not reached at time of analysis as most participants were still in response.
|
SECONDARY outcome
Timeframe: 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)Population: Participants who received at least 1 dose of talimogene laherparepvec.
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=111 Participants
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.
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|---|---|
|
Time to Treatment Failure
Primary completion
|
8.1 months
Interval 5.4 to 10.9
|
|
Time to Treatment Failure
Final analysis
|
8.1 months
Interval 5.4 to 11.0
|
SECONDARY outcome
Timeframe: 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)Population: Participants who received at least 1 dose of talimogene laherparepvec.
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=111 Participants
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.
|
|---|---|
|
Durable Response Rate
Primary completion
|
13.5 percentage of participants
Interval 7.8 to 21.3
|
|
Durable Response Rate
Final analysis
|
21.6 percentage of participants
Interval 14.4 to 30.4
|
SECONDARY outcome
Timeframe: 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)Population: Participants who received at least 1 dose of talimogene laherparepvec.
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=111 Participants
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.
|
|---|---|
|
Overall Survival
Primary completion
|
NA months
Median overall survival was not reached due to the low number of deaths.
|
|
Overall Survival
Final analysis
|
NA months
Interval 34.9 to
Median overall survival was not reached due to the low number of deaths.
|
SECONDARY outcome
Timeframe: 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.Population: Participants who received at least 1 dose of talimogene laherparepvec with an objective response (CR or PR)
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=32 Participants
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.
|
|---|---|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 96 day 1
|
-16.505 cm²
Standard Deviation 15.244
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 102 day 1
|
-17.793 cm²
Standard Deviation 18.413
|
|
Change From Baseline in Tumor Burden
Baseline
|
16.420 cm²
Standard Deviation 41.269
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 6 day 1
|
-5.883 cm²
Standard Deviation 12.158
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 12 day 1
|
-10.085 cm²
Standard Deviation 22.862
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 18 day 1
|
-13.074 cm²
Standard Deviation 27.798
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 24 day 1
|
-21.407 cm²
Standard Deviation 42.221
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 30 day 1
|
-30.404 cm²
Standard Deviation 55.593
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 36 day 1
|
-31.803 cm²
Standard Deviation 69.358
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 42 day 1
|
-10.208 cm²
Standard Deviation 14.188
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 48 day 1
|
-11.396 cm²
Standard Deviation 14.885
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 54 day 1
|
-11.693 cm²
Standard Deviation 15.720
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 60 day 1
|
-13.122 cm²
Standard Deviation 17.791
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 66 day 1
|
-16.797 cm²
Standard Deviation 14.659
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 72 day 1
|
-16.797 cm²
Standard Deviation 14.659
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 78 day 1
|
-16.858 cm²
Standard Deviation 14.730
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 84 day 1
|
-17.022 cm²
Standard Deviation 14.992
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 90 day 1
|
-13.916 cm²
Standard Deviation 14.381
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 108 day 1
|
-17.733 cm²
Standard Deviation 18.426
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 114 day 1
|
-1.694 cm²
Standard Deviation NA
Only 1 participant had non-missing data at this time-point, so standard deviation could not be calculated.
|
|
Change From Baseline in Tumor Burden
Change from baseline at Cycle 120 day 1
|
-39.930 cm²
Standard Deviation NA
Only 1 participant had non-missing data at this time-point, so standard deviation could not be calculated.
|
SECONDARY outcome
Timeframe: 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)Population: Participants who received at least 1 dose of talimogene laherparepvec.
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.
Outcome measures
| Measure |
Talimogene Laherparepvec
n=111 Participants
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.
|
|---|---|
|
Number of Participants With Adverse Events
Any adverse event
|
108 Participants
|
|
Number of Participants With Adverse Events
Adverse events ≥ grade 3
|
38 Participants
|
|
Number of Participants With Adverse Events
Adverse events ≥ grade 4
|
11 Participants
|
|
Number of Participants With Adverse Events
Serious adverse events
|
33 Participants
|
|
Number of Participants With Adverse Events
AE leading to discontinuation of study drug
|
4 Participants
|
|
Number of Participants With Adverse Events
Fatal adverse events
|
4 Participants
|
|
Number of Participants With Adverse Events
Treatment-related adverse events
|
93 Participants
|
|
Number of Participants With Adverse Events
Treatment-related adverse events ≥ grade 3
|
11 Participants
|
|
Number of Participants With Adverse Events
Treatment-related adverse events ≥ grade 4
|
2 Participants
|
|
Number of Participants With Adverse Events
Treatment-related serious adverse events
|
9 Participants
|
|
Number of Participants With Adverse Events
TRAE leading to discontinuation of study drug
|
3 Participants
|
|
Number of Participants With Adverse Events
Treatment-related fatal adverse events
|
0 Participants
|
Adverse Events
Talimogene Laherparepvec
Serious events: 33 serious events
Other events: 97 other events
Deaths: 41 deaths
Serious adverse events
| Measure |
Talimogene Laherparepvec
n=111 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Cardiac failure
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Gastrointestinal disorders
Faecaloma
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
General disorders
General physical health deterioration
|
1.8%
2/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
General disorders
Pyrexia
|
1.8%
2/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Immune system disorders
Cytokine release syndrome
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Infections and infestations
Bronchitis
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Infections and infestations
Pneumonia
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Injury, poisoning and procedural complications
Fall
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Investigations
Medical observation
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.8%
2/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
1.8%
2/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lymph nodes
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to pleura
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic malignant melanoma
|
2.7%
3/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Nodular melanoma
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Psychiatric disorders
Anxiety
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Psychiatric disorders
Paranoia
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
General disorders
Oedema peripheral
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neurofibrosarcoma
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Surgical and medical procedures
Cardiac pacemaker replacement
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Blood and lymphatic system disorders
Anaemia
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Gastrointestinal disorders
Ileus
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Infections and infestations
COVID-19 pneumonia
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
|
0.90%
1/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
Other adverse events
| Measure |
Talimogene Laherparepvec
n=111 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
6.3%
7/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Gastrointestinal disorders
Diarrhoea
|
12.6%
14/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Gastrointestinal disorders
Nausea
|
23.4%
26/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Gastrointestinal disorders
Vomiting
|
9.9%
11/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
General disorders
Asthenia
|
16.2%
18/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
General disorders
Chills
|
27.0%
30/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
General disorders
Fatigue
|
21.6%
24/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
General disorders
Influenza like illness
|
26.1%
29/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
General disorders
Injection site pain
|
17.1%
19/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
General disorders
Pain
|
6.3%
7/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
General disorders
Pyrexia
|
46.8%
52/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.2%
8/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
18.0%
20/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.1%
9/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.4%
16/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Nervous system disorders
Headache
|
18.9%
21/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.2%
8/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
General disorders
Oedema peripheral
|
6.3%
7/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Infections and infestations
Nasopharyngitis
|
9.9%
11/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Blood and lymphatic system disorders
Anaemia
|
7.2%
8/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.4%
6/111 • Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER