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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-001146-13 | EudraCT Number |
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This is a phase 2, multicenter, randomized, open-label study to estimate the efficacy of talimogene laherparepvec as a neoadjuvant treatment followed by surgery compared to surgery alone in subjects with completely resectable stage IIIB, IIIC, or IVM1a melanoma.
This is a phase 2, multicenter, randomized, open-label study to estimate the efficacy of talimogene laherparepvec as a neoadjuvant treatment followed by surgery compared to surgery alone in subjects with completely resectable stage IIIB, IIIC, or IVM1a melanoma.
Arm 1: Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s).
Arm 2: Immediate surgical resection of melanoma tumor lesion(s) Following surgery, adjuvant systemic therapy and/or radiotherapy may be administered at the investigator's discretion and per the institutional standard of care.
Subjects will be followed for safety approximately 30 (+15) days after surgery and for disease recurrence, subsequent anticancer therapy, and survival every 3 months (±30 days) for first 3 years after the end of the safety follow-up period and then every 6 months (±30 days) until death, subject withdraws full consent, or up to 5 years after the last subject is randomized.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Surgery | Other | Surgical resection of melanoma tumor lesion(s) |
|
| Talimogene Laherparepvec | Experimental | Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Talimogene Laherparepvec | Drug | Talimogene laherparepvec will be administered by intralesional injection into the injectable cutaneous, subcutaneous, and nodal tumors initially at a dose of 10^6 plaque forming units (PFU)/mL at day 1 of week 1 followed by a dose of 10^8 PFU/mL at day 1 (±3 days) of week 4, 6, 8, 10 and 12 or until all injectable tumors have disappeared, or intolerance of study treatment or in the opinion of the investigator, immediate surgical resection or any other treatment for melanoma is warranted, whichever occurs first. |
| Measure | Description | Time Frame |
|---|---|---|
| Recurrence-Free Survival (RFS) | Recurrence free survival (RFS) is defined as the time from randomization to the date of event, and is presented as a Kaplan Meier estimate of time to events. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without a histopathology tumor-free margin (R0) surgical outcome or those who withdrew prior to surgery were considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment. | 24 months after last participant was randomized (data cutoff date of 30 April 2019) |
| Measure | Description | Time Frame |
|---|---|---|
| RFS | Recurrence free survival (RFS) is defined as the time from randomization to the date of event, and is presented as a Kaplan Meier estimate of time to events. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without a histopathology tumor-free margin (R0) surgical outcome or those who withdrew prior to surgery were considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment. |
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Inclusion Criteria:
Exclusion Criteria:
Other criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Birmingham | Alabama | 35249 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34608333 | Background | Dummer R, Gyorki DE, Hyngstrom J, Berger AC, Conry R, Demidov L, Sharma A, Treichel SA, Radcliffe H, Gorski KS, Anderson A, Chan E, Faries M, Ross MI. Neoadjuvant talimogene laherparepvec plus surgery versus surgery alone for resectable stage IIIB-IVM1a melanoma: a randomized, open-label, phase 2 trial. Nat Med. 2021 Oct;27(10):1789-1796. doi: 10.1038/s41591-021-01510-7. Epub 2021 Oct 4. | |
| 36648215 |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
Participants were randomized 1:1 to receive either talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesions or immediate surgical resection of melanoma tumor lesion(s). Randomization was stratified by disease stage and planned adjuvant therapy.
This study was conducted at 35 centers in Australia, Brazil, Europe, Russia, and the United States. Participants were enrolled between 03 February 2015 and 28 April 2022.
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| ID | Title | Description |
|---|---|---|
| FG000 | Surgery | Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6. |
| FG001 | Talimogene Laherparepvec Plus Surgery | Talimogene laherparepvec up to 4.0 mL of 10^6 PFU/mL followed by up to 4.0 mL of 10^8 PFU/mL administered 21 (+5) days after the initial dose. Subsequent doses up to 4.0 mL of 10^8 PFU/mL every 14 (± 3) days until Week 12, all injectable tumors have disappeared, or intolerance of study treatment, whichever occurs first. Followed by surgical resection of melanoma lesions(s) anytime during Weeks 13 to 18. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 23, 2018 | Apr 21, 2020 |
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| Immediate surgical resection of melanoma lesion(s) | Procedure | Surgical resection of melanoma tumor lesion(s) will be performed after randomization any time during weeks 1 to 6. |
|
| 5 years after the last participant was randomized (last subject last visit occurred 28 April 2022) |
| Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years | Kaplan-Meier estimates of the percentage of participants with RFS at 1 year, 2 years, 3 years, and 5 years from randomization. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment. Rate is presented as the percentage of participants with RFS at given time point. | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
| Histopathology Tumor-Free Margin (R0) Surgical Resection Rate | Histopathology tumor-free margin (R0) surgical resection is defined by pathologist as absence of ink on the tumor for all disease. Rate is presented as the percentage of participants with histopathology tumor-free margin (R0) surgical resection. | 18 weeks after last participant randomized (data cutoff date of 30 April 2019) |
| Pathological Complete Response (pCR) Rate | Pathological Complete Response (pCR) is defined as no evidence of viable tumor cells on complete pathological evaluation of the surgical specimen per institutional standards of care. Rate is presented as the percentage of participants with pCR. | 18 weeks after last participant randomized (data cutoff date of 30 April 2019) |
| Local Recurrence-Free Survival (LRFS) | Local recurrence-free survival (LRFS) is defined as the time from randomization to the earlier date of the first of local disease recurrence or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Local recurrence is defined as histologically or cytologically confirmed reappearance of melanoma in the area of up to 2 cm from the scar from the surgical excision or at the edge of the skin graft if that was used for closure. | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
| Regional Recurrence-Free Survival (RRFS) | Regional recurrence-free survival (RRFS) is defined as the time from randomization to the date of the first of regional disease recurrence or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Regional recurrence excludes local recurrence and is defined as histologically, cytologically, or radiographically confirmed reappearance of melanoma in the regional lymph node basin. | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
| Distant Metastases-Free Survival (DMFS) | Distant metastases-free survival (DMFS) is defined as the time from randomization to the date of the first of distant metastases or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Distant metastases exclude local and regional recurrence and will include distant cutaneous/subcutaneous metastases, distant nodal metastases, or visceral, central nervous system, brain, or bone metastases. | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
| Overall Survival (Kaplan-Meier) | Overall Survival (OS) is defined as the time from randomization to the date of death due to any cause. | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
| Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years | Kaplan-Meier estimates of the percentage of participants alive at 1 year, 2 years, 3 years, and 5 years from randomization. | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
| Best Overall Tumor Response Per Investigator Response Rate (Talimogene Laherparepvec Arm Only) | Response was assessed based on the response of the index lesions and nonindex lesions as described in protocol-defined World Health Organization (WHO) criteria (for complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]), and presence or absence of new lesions. Best response for a participant is the best overall response observed across all time points. Response rate is reported as the percentage of participants with the best overall response (per investigator) of CR or PR. CR: complete disappearance of all index lesions, including any new measurable tumor lesions which might have appeared. PR: ≥ 50% reduction in the sum of the products of the 2 largest perpendicular diameters of all index lesions and new measurable lesions, if applicable, at the time of assessment as compared to the sum of the products of the perpendicular diameters of all index lesions at baseline. | 18 months after last participant randomized (data cutoff date of 30 April 2019). |
| Lesion Objective Response Rate: Injected Lesions (Talimogene Laherparepvec Arm Only) | The investigator-assessed tumor response rate for injected lesions, reported as the percentage of evaluable lesions in response. A lesion is in response if the decrease in tumor area is ≥ 50%. | 18 months after last participant randomized (data cutoff date of 30 April 2019). |
| Lesion Objective Response Rate: Uninjected Lesions (Talimogene Laherparepvec Arm Only) | The investigator-assessed tumor response rate for uninjected lesions, reported as the percentage of evaluable lesions in response. A lesion is in response if the decrease in tumor area is ≥ 50%. | 18 months after last participant randomized (data cutoff date of 30 April 2019). |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Adverse event (AE): any untoward medical occurrence that does not necessarily have a causal relationship with study treatment. SAE: AE meeting 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. Event severity grades: 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). Treatment begins when the first dose of protocol-required therapies is administered to a participant (Talimogene Laherparepvec Arm) or the participant undergoes surgery (Surgery Arm). Events are reported from first day of study drug or the surgery through 30 days after the last administration of talimogene laherparepvec or 30 days after the surgical resection of melanoma tumor lesion(s), whichever is later. | Adverse Events are reported from first day of study drug or the surgery through 30 days after the last dose of study drug or 30 days after the surgery, whichever is later. Median duration of treatment was 11.14 weeks (range 0.1 to 12.3 weeks). |
| Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Adverse event (AE): any untoward medical occurrence that does not necessarily have a causal relationship with study treatment. SAE: AE meeting 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. Event severity grades: 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). Treatment begins when the first dose of protocol-required therapies is administered to a participant (Talimogene Laherparepvec Arm) or the participant undergoes surgery (Surgery Arm). Events are reported from first day of study drug or the surgery through 30 days after the last administration of talimogene laherparepvec or 30 days after the surgical resection of melanoma tumor lesion(s), whichever is later. | Adverse Events are reported from first day of study drug or the surgery through 30 days after the last administration of talimogene laherparepvec or 30 days after the surgical resection of melanoma tumor lesion(s), whichever is later. |
| Duarte |
| California |
| 91010 |
| United States |
| Research Site | Orange | California | 92868 | United States |
| Research Site | San Francisco | California | 94115 | United States |
| Research Site | Santa Monica | California | 90404 | United States |
| Research Site | Daytona Beach | Florida | 32117 | United States |
| Research Site | Gainesville | Florida | 32610 | United States |
| Research Site | Tampa | Florida | 33612 | United States |
| Research Site | Louisville | Kentucky | 40202 | United States |
| Research Site | Worcester | Massachusetts | 01655 | United States |
| Research Site | Omaha | Nebraska | 68130 | United States |
| Research Site | New Brunswick | New Jersey | 08903 | United States |
| Research Site | New York | New York | 10029 | United States |
| Research Site | New York | New York | 10032 | United States |
| Research Site | Chapel Hill | North Carolina | 27599 | United States |
| Research Site | Columbus | Ohio | 43210 | United States |
| Research Site | Philadelphia | Pennsylvania | 19107 | United States |
| Research Site | Memphis | Tennessee | 38163 | United States |
| Research Site | Dallas | Texas | 75230 | United States |
| Research Site | Dallas | Texas | 75390 | United States |
| Research Site | Houston | Texas | 77030 | United States |
| Research Site | Salt Lake City | Utah | 84112 | United States |
| Research Site | North Sydney | New South Wales | 2060 | Australia |
| Research Site | Woodville South | South Australia | 5011 | Australia |
| Research Site | Heidelberg | Victoria | 3084 | Australia |
| Research Site | Florianópolis | Santa Catarina | 88034-000 | Brazil |
| Research Site | Barretos | São Paulo | 14784-400 | Brazil |
| Research Site | Rio de Janeiro | 20220-410 | Brazil |
| Research Site | Dijon | 21034 | France |
| Research Site | Marseille | 13385 | France |
| Research Site | Paris | 75010 | France |
| Research Site | Pierre-Bénite | 69495 | France |
| Research Site | Toulouse | 31059 | France |
| Research Site | Athens | 11527 | Greece |
| Research Site | Heraklion - Crete | 71110 | Greece |
| Research Site | Poznan | 60-856 | Poland |
| Research Site | Warsaw | 02-781 | Poland |
| Research Site | Wroclaw | 50-368 | Poland |
| Research Site | Moscow | 115478 | Russia |
| Research Site | Saint Petersburg | 197022 | Russia |
| Research Site | Saint Petersburg | 197758 | Russia |
| Research Site | Málaga | Andalusia | 29010 | Spain |
| Research Site | Pamplona | Navarre | 31008 | Spain |
| Research Site | Madrid | 28009 | Spain |
| Research Site | Chur | 7000 | Switzerland |
| Research Site | Zurich | 8091 | Switzerland |
| Derived |
| Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2. |
| COMPLETED |
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| NOT COMPLETED |
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Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
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| ID | Title | Description |
|---|---|---|
| BG000 | Surgery | Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6. |
| BG001 | Talimogene Laherparepvec Plus Surgery | Talimogene laherparepvec up to 4.0 mL of 10^6 PFU/mL followed by up to 4.0 mL of 10^8 PFU/mL administered 21 (+5) days after the initial dose. Subsequent doses up to 4.0 mL of 10^8 PFU/mL every 14 (± 3) days until Week 12, all injectable tumors have disappeared, or intolerance of study treatment, whichever occurs first. Followed by surgical resection of melanoma lesions(s) anytime during Weeks 13 to 18. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Stratification Factor: Disease Stage | The clinical participants were staged according to the American Joint Committee of Cancer (AJCC) 7th edition Melanoma Staging System, which combines tumor staging, nodal staging and metastasis to derive an overall stage. The order of prognostication is as follows: stage IIIB (better prognosis) > stage IIIC > stage IV M1a (worse prognosis). Randomization was stratified by disease stage and planned adjuvant therapy (adjuvant systemic therapy with or without radiotherapy vs radiotherapy without adjuvant systemic therapy vs none). | Number | participants |
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| Stratification Factor: Planned Adjuvant Therapy | Randomization was stratified by disease stage (IIIB nodal vs IIIB in-transit vs IIIC nodal vs IIIC in-transit with nodal vs IVM1a) and planned adjuvant therapy (adjuvant systemic therapy with (W/) or without (W/O) radiotherapy vs radiotherapy without (W/O) adjuvant systemic therapy vs none). | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Recurrence-Free Survival (RFS) | Recurrence free survival (RFS) is defined as the time from randomization to the date of event, and is presented as a Kaplan Meier estimate of time to events. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without a histopathology tumor-free margin (R0) surgical outcome or those who withdrew prior to surgery were considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Median | 80% Confidence Interval | months | 24 months after last participant was randomized (data cutoff date of 30 April 2019) |
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| Secondary | RFS | Recurrence free survival (RFS) is defined as the time from randomization to the date of event, and is presented as a Kaplan Meier estimate of time to events. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without a histopathology tumor-free margin (R0) surgical outcome or those who withdrew prior to surgery were considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Median | 80% Confidence Interval | months | 5 years after the last participant was randomized (last subject last visit occurred 28 April 2022) |
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| Secondary | Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years | Kaplan-Meier estimates of the percentage of participants with RFS at 1 year, 2 years, 3 years, and 5 years from randomization. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment. Rate is presented as the percentage of participants with RFS at given time point. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Number | 80% Confidence Interval | percentage of participants | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
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| Secondary | Histopathology Tumor-Free Margin (R0) Surgical Resection Rate | Histopathology tumor-free margin (R0) surgical resection is defined by pathologist as absence of ink on the tumor for all disease. Rate is presented as the percentage of participants with histopathology tumor-free margin (R0) surgical resection. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Number | 80% Confidence Interval | percentage of participants | 18 weeks after last participant randomized (data cutoff date of 30 April 2019) |
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| Secondary | Pathological Complete Response (pCR) Rate | Pathological Complete Response (pCR) is defined as no evidence of viable tumor cells on complete pathological evaluation of the surgical specimen per institutional standards of care. Rate is presented as the percentage of participants with pCR. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Number | 80% Confidence Interval | percentage of participants | 18 weeks after last participant randomized (data cutoff date of 30 April 2019) |
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| Secondary | Local Recurrence-Free Survival (LRFS) | Local recurrence-free survival (LRFS) is defined as the time from randomization to the earlier date of the first of local disease recurrence or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Local recurrence is defined as histologically or cytologically confirmed reappearance of melanoma in the area of up to 2 cm from the scar from the surgical excision or at the edge of the skin graft if that was used for closure. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Median | 80% Confidence Interval | months | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
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| Secondary | Regional Recurrence-Free Survival (RRFS) | Regional recurrence-free survival (RRFS) is defined as the time from randomization to the date of the first of regional disease recurrence or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Regional recurrence excludes local recurrence and is defined as histologically, cytologically, or radiographically confirmed reappearance of melanoma in the regional lymph node basin. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Median | 80% Confidence Interval | months | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
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| Secondary | Distant Metastases-Free Survival (DMFS) | Distant metastases-free survival (DMFS) is defined as the time from randomization to the date of the first of distant metastases or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Distant metastases exclude local and regional recurrence and will include distant cutaneous/subcutaneous metastases, distant nodal metastases, or visceral, central nervous system, brain, or bone metastases. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Median | 80% Confidence Interval | months | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
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| Secondary | Overall Survival (Kaplan-Meier) | Overall Survival (OS) is defined as the time from randomization to the date of death due to any cause. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Median | 80% Confidence Interval | months | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
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| Secondary | Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years | Kaplan-Meier estimates of the percentage of participants alive at 1 year, 2 years, 3 years, and 5 years from randomization. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Number | 80% Confidence Interval | percentage of participants | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) |
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| Secondary | Best Overall Tumor Response Per Investigator Response Rate (Talimogene Laherparepvec Arm Only) | Response was assessed based on the response of the index lesions and nonindex lesions as described in protocol-defined World Health Organization (WHO) criteria (for complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]), and presence or absence of new lesions. Best response for a participant is the best overall response observed across all time points. Response rate is reported as the percentage of participants with the best overall response (per investigator) of CR or PR. CR: complete disappearance of all index lesions, including any new measurable tumor lesions which might have appeared. PR: ≥ 50% reduction in the sum of the products of the 2 largest perpendicular diameters of all index lesions and new measurable lesions, if applicable, at the time of assessment as compared to the sum of the products of the perpendicular diameters of all index lesions at baseline. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Number | 80% Confidence Interval | percentage of participants | 18 months after last participant randomized (data cutoff date of 30 April 2019). |
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| Secondary | Lesion Objective Response Rate: Injected Lesions (Talimogene Laherparepvec Arm Only) | The investigator-assessed tumor response rate for injected lesions, reported as the percentage of evaluable lesions in response. A lesion is in response if the decrease in tumor area is ≥ 50%. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Number | 80% Confidence Interval | percentage of lesions | 18 months after last participant randomized (data cutoff date of 30 April 2019). |
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| Secondary | Lesion Objective Response Rate: Uninjected Lesions (Talimogene Laherparepvec Arm Only) | The investigator-assessed tumor response rate for uninjected lesions, reported as the percentage of evaluable lesions in response. A lesion is in response if the decrease in tumor area is ≥ 50%. | Intent to Treat Analysis Set: all participants who were randomized to either treatment group. | Posted | Number | 80% Confidence Interval | percentage of lesions | 18 months after last participant randomized (data cutoff date of 30 April 2019). |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Adverse event (AE): any untoward medical occurrence that does not necessarily have a causal relationship with study treatment. SAE: AE meeting 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. Event severity grades: 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). Treatment begins when the first dose of protocol-required therapies is administered to a participant (Talimogene Laherparepvec Arm) or the participant undergoes surgery (Surgery Arm). Events are reported from first day of study drug or the surgery through 30 days after the last administration of talimogene laherparepvec or 30 days after the surgical resection of melanoma tumor lesion(s), whichever is later. | Safety Analysis Set: all participants who received talimogene laherparepvec (TL) or surgical resection of melanoma tumor lesion(s). | Posted | Count of Participants | Participants | Adverse Events are reported from first day of study drug or the surgery through 30 days after the last dose of study drug or 30 days after the surgery, whichever is later. Median duration of treatment was 11.14 weeks (range 0.1 to 12.3 weeks). |
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| Secondary | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Adverse event (AE): any untoward medical occurrence that does not necessarily have a causal relationship with study treatment. SAE: AE meeting 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. Event severity grades: 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). Treatment begins when the first dose of protocol-required therapies is administered to a participant (Talimogene Laherparepvec Arm) or the participant undergoes surgery (Surgery Arm). Events are reported from first day of study drug or the surgery through 30 days after the last administration of talimogene laherparepvec or 30 days after the surgical resection of melanoma tumor lesion(s), whichever is later. | Safety Analysis Set: all participants who received talimogene laherparepvec (TL). | Posted | Count of Participants | Participants | Adverse Events are reported from first day of study drug or the surgery through 30 days after the last administration of talimogene laherparepvec or 30 days after the surgical resection of melanoma tumor lesion(s), whichever is later. |
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Adverse Events are reported from first day of study drug or the surgery through 30 days after the last dose of study drug or 30 days after the surgery, whichever is later. Median duration of treatment was 11.14 weeks (range 0.1 to 12.3 weeks). All-cause mortality was reported from enrollment through end of follow-up (up to 5 years after randomization).
All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all randomized subjects who received talimogene laherparepvec or surgical resection of melanoma tumor lesion(s).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Surgery | Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6. | 26 | 74 | 2 | 69 | 14 | 69 |
| EG001 | TALIMOGENE LAHERPAREPVEC PLUS SURGERY | Talimogene laherparepvec up to 4.0 mL of 10^6 PFU/mL followed by up to 4.0 mL of 10^8 PFU/mL administered 21 (+5) days after the initial dose. Subsequent doses up to 4.0 mL of 10^8 PFU/mL every 14 (± 3) days until Week 12, all injectable tumors have disappeared, or intolerance of study treatment, whichever occurs first. Followed by surgical resection of melanoma lesions(s) anytime during Weeks 13 to 18. | 16 | 76 | 13 | 73 | 62 | 73 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Cholecystitis | Hepatobiliary disorders | MedDRA 24.1 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Postoperative wound infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Wound abscess | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Glioblastoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 24.1 | Systematic Assessment |
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| Cerebral ischaemia | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
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| Anembryonic gestation | Pregnancy, puerperium and perinatal conditions | MedDRA 24.1 | Systematic Assessment |
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| Device occlusion | Product Issues | MedDRA 24.1 | Systematic Assessment |
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| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Neck dissection | Surgical and medical procedures | MedDRA 24.1 | Systematic Assessment |
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| Peripheral embolism | Vascular disorders | MedDRA 24.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Chills | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 14, 2019 | Apr 21, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| C000629782 | talimogene laherparepvec |
Not provided
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Stage IIIB In-Transit |
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| Stage IIIC Nodal |
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| Stage IIIC In-Transit With Nodal |
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| Stage IV M1a |
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| Radiotherapy W/O Adjuvant Systemic Therapy |
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| None |
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| OG001 | Talimogene Laherparepvec: Pre-Surgery | Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s). Limited to participants who received at least 1 dose of talimogene laherparepvec and protocol-specified surgery. |
| OG002 | Talimogene Laherparepvec: Post-Surgery | Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s). Limited to participants who received at least 1 dose of talimogene laherparepvec and protocol-specified surgery. |
| OG003 | Talimogene Laherparepvec Plus Surgery | Talimogene laherparepvec up to 4.0 mL of 10^6 PFU/mL followed by up to 4.0 mL of 10^8 PFU/mL administered 21 (+5) days after the initial dose. Subsequent doses up to 4.0 mL of 10^8 PFU/mL every 14 (± 3) days until Week 12, all injectable tumors have disappeared, or intolerance of study treatment, whichever occurs first. Followed by surgical resection of melanoma lesions(s) anytime during Weeks 13 to 18. |
|
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| OG001 | Talimogene Laherparepvec: Post-Surgery | Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s). Limited to participants who received at least 1 dose of talimogene laherparepvec and protocol-specified surgery. |
| OG002 | Talimogene Laherparepvec Plus Surgery | Talimogene laherparepvec up to 4.0 mL of 10^6 PFU/mL followed by up to 4.0 mL of 10^8 PFU/mL administered 21 (+5) days after the initial dose. Subsequent doses up to 4.0 mL of 10^8 PFU/mL every 14 (± 3) days until Week 12, all injectable tumors have disappeared, or intolerance of study treatment, whichever occurs first. Followed by surgical resection of melanoma lesions(s) anytime during Weeks 13 to 18. |
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