Completely Resectable Stage IIIB, IIIC, or IVM1a Melanoma
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGTalimogene Laherparepvec
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.
PROCEDUREImmediate surgical resection of melanoma lesion(s)
Surgical resection of melanoma tumor lesion(s) will be performed after randomization any time during weeks 1 to 6.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of stage IIIB, IIIC or IVM1a melanoma eligible for complete surgical resection. * Prior systemic, regional and radiation anticancer therapies for melanoma must have been completed at least 3 months prior to randomization. * Subject must have measurable disease and must be a candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm. * Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and must have a serum lactate dehydrogenase (LDH) ≤ 1.0 X upper limit of normal and adequate hematologic, hepatic, renal, and coagulation organ function- Other criteria may apply
Exclusion criteria
* Subject must not have primary ocular or mucosal melanoma, or history or evidence of melanoma associated with immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia). * Subject must not have history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease. * Subject must not have evidence of clinically significant immunosuppression or active herpetic skin lesions or prior complications of herpes simplex type 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis) and must not require intermittent or chronic systemic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use. * Subject known to have acute or chronic active hepatitis B, hepatitis C, or human immunodeficiency virus infection will also be excluded. * Subject must not have been treated previously with talimogene laherparepvec or tumor vaccine. Other criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-Free Survival (RFS) | 24 months after last participant was randomized (data cutoff date of 30 April 2019) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) | 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. |
| Histopathology Tumor-Free Margin (R0) Surgical Resection Rate | 18 weeks after last participant randomized (data cutoff date of 30 April 2019) | 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. |
| Pathological Complete Response (pCR) Rate | 18 weeks after last participant randomized (data cutoff date of 30 April 2019) | 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. |
| Local Recurrence-Free Survival (LRFS) | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) | 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. |
| Regional Recurrence-Free Survival (RRFS) | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) | 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. |
| Distant Metastases-Free Survival (DMFS) | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) | 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. |
| RFS | 5 years after the last participant was randomized (last subject last visit occurred 28 April 2022) | 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. |
| Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) | Kaplan-Meier estimates of the percentage of participants alive at 1 year, 2 years, 3 years, and 5 years from randomization. |
| Best Overall Tumor Response Per Investigator Response Rate (Talimogene Laherparepvec Arm Only) | 18 months after last participant randomized (data cutoff date of 30 April 2019). | 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. |
| Lesion Objective Response Rate: Injected Lesions (Talimogene Laherparepvec Arm Only) | 18 months after last participant randomized (data cutoff date of 30 April 2019). | 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%. |
| Lesion Objective Response Rate: Uninjected Lesions (Talimogene Laherparepvec Arm Only) | 18 months after last participant randomized (data cutoff date of 30 April 2019). | 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%. |
| 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 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). | 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. |
| Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | 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. | 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. |
| Overall Survival (Kaplan-Meier) | 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022) | Overall Survival (OS) is defined as the time from randomization to the date of death due to any cause. |
Countries
Australia, Brazil, France, Greece, Poland, Russia, Spain, Switzerland, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Surgery Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6. | 74 |
| 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. | 76 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 26 | 16 |
| Overall Study | Decision by Sponsor | 1 | 1 |
| Overall Study | Lost to Follow-up | 4 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 8 |
Baseline characteristics
| Characteristic | Surgery | Total | Talimogene Laherparepvec Plus Surgery |
|---|---|---|---|
| Age, Continuous | 59.1 years STANDARD_DEVIATION 16.1 | 60.9 years STANDARD_DEVIATION 14.5 | 62.6 years STANDARD_DEVIATION 12.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants | 139 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 73 Participants | 146 Participants | 73 Participants |
| Sex: Female, Male Female | 27 Participants | 54 Participants | 27 Participants |
| Sex: Female, Male Male | 47 Participants | 96 Participants | 49 Participants |
| Stratification Factor: Disease Stage Stage IIIB In-Transit | 17 participants | 33 participants | 16 participants |
| Stratification Factor: Disease Stage Stage IIIB Nodal | 14 participants | 29 participants | 15 participants |
| Stratification Factor: Disease Stage Stage IIIC In-Transit With Nodal | 17 participants | 34 participants | 17 participants |
| Stratification Factor: Disease Stage Stage IIIC Nodal | 14 participants | 27 participants | 13 participants |
| Stratification Factor: Disease Stage Stage IV M1a | 12 participants | 27 participants | 15 participants |
| Stratification Factor: Planned Adjuvant Therapy Adjuvant Systemic Therapy W/ or W/O Radiotherapy | 9 participants | 18 participants | 9 participants |
| Stratification Factor: Planned Adjuvant Therapy None | 62 participants | 126 participants | 64 participants |
| Stratification Factor: Planned Adjuvant Therapy Radiotherapy W/O Adjuvant Systemic Therapy | 3 participants | 6 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 26 / 74 | 16 / 76 |
| other Total, other adverse events | 14 / 69 | 62 / 73 |
| serious Total, serious adverse events | 2 / 69 | 13 / 73 |
Outcome results
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.
Time frame: 24 months after last participant was randomized (data cutoff date of 30 April 2019)
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Surgery | Recurrence-Free Survival (RFS) | 0.0 months |
| Talimogene Laherparepvec Plus Surgery | Recurrence-Free Survival (RFS) | 0.0 months |
p-value: 0.0780% CI: [0.58, 0.96]Log Rank
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.
Time frame: 18 months after last participant randomized (data cutoff date of 30 April 2019).
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Surgery | Best Overall Tumor Response Per Investigator Response Rate (Talimogene Laherparepvec Arm Only) | 13.2 percentage of participants |
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.
Time frame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Surgery | Distant Metastases-Free Survival (DMFS) | 0.0 months |
| Talimogene Laherparepvec Plus Surgery | Distant Metastases-Free Survival (DMFS) | 0.0 months |
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.
Time frame: 18 weeks after last participant randomized (data cutoff date of 30 April 2019)
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Surgery | Histopathology Tumor-Free Margin (R0) Surgical Resection Rate | 37.8 percentage of participants |
| Talimogene Laherparepvec Plus Surgery | Histopathology Tumor-Free Margin (R0) Surgical Resection Rate | 42.1 percentage of participants |
p-value: 0.59480% CI: [-6.9, 15.3]Chi-squared
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.
Time frame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Surgery | Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years | Year 1 | 85.92 percentage of participants |
| Surgery | Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years | Year 3 | 71.59 percentage of participants |
| Surgery | Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years | Year 2 | 77.44 percentage of participants |
| Surgery | Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years | Year 5 | 62.29 percentage of participants |
| Talimogene Laherparepvec Plus Surgery | Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years | Year 2 | 88.94 percentage of participants |
| Talimogene Laherparepvec Plus Surgery | Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years | Year 1 | 95.89 percentage of participants |
| Talimogene Laherparepvec Plus Surgery | Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years | Year 5 | 77.32 percentage of participants |
| Talimogene Laherparepvec Plus Surgery | Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years | Year 3 | 83.27 percentage of participants |
p-value: 0.0580% CI: [0.36, 0.81]Log Rank
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.
Time frame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Surgery | Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years | RFS at 1 Year | 21.95 percentage of participants |
| Surgery | Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years | RFS at 2 Years | 16.88 percentage of participants |
| Surgery | Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years | RFS at 3 Years | 16.88 percentage of participants |
| Surgery | Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years | RFS at 5 Years | 15.19 percentage of participants |
| Talimogene Laherparepvec Plus Surgery | Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years | RFS at 5 Years | 22.32 percentage of participants |
| Talimogene Laherparepvec Plus Surgery | Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years | RFS at 1 Year | 33.73 percentage of participants |
| Talimogene Laherparepvec Plus Surgery | Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years | RFS at 3 Years | 28.11 percentage of participants |
| Talimogene Laherparepvec Plus Surgery | Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years | RFS at 2 Years | 29.51 percentage of participants |
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%.
Time frame: 18 months after last participant randomized (data cutoff date of 30 April 2019).
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Surgery | Lesion Objective Response Rate: Injected Lesions (Talimogene Laherparepvec Arm Only) | 26.3 percentage of lesions |
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%.
Time frame: 18 months after last participant randomized (data cutoff date of 30 April 2019).
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Surgery | Lesion Objective Response Rate: Uninjected Lesions (Talimogene Laherparepvec Arm Only) | 3.9 percentage of lesions |
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.
Time frame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Surgery | Local Recurrence-Free Survival (LRFS) | 0.0 months |
| Talimogene Laherparepvec Plus Surgery | Local Recurrence-Free Survival (LRFS) | 0.0 months |
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.
Time frame: 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.
Population: Safety Analysis Set: all participants who received talimogene laherparepvec (TL).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Grade ≥4 | 0 Participants |
| Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Nonserious | 0 Participants |
| Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to Interruption of TL | 0 Participants |
| Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Serious TEAEs | 1 Participants |
| Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Grade ≥2 | 13 Participants |
| Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to DC of TL | 1 Participants |
| Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | All TEAEs | 51 Participants |
| Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Serious | 1 Participants |
| Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Grade ≥3 | 1 Participants |
| Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Fatal Adverse Events | 0 Participants |
| Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered | 1 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to DC of TL | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | All TEAEs | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Grade ≥2 | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Grade ≥3 | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Grade ≥4 | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Serious TEAEs | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to Interruption of TL | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Serious | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Nonserious | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Fatal Adverse Events | 0 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Grade ≥3 | 3 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Fatal Adverse Events | 0 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered | 1 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Grade ≥2 | 20 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Nonserious | 0 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Serious | 1 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Serious TEAEs | 2 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to DC of TL | 1 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Grade ≥4 | 0 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | All TEAEs | 64 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions | Leading to Interruption of TL | 0 Participants |
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.
Time frame: 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).
Population: Safety Analysis Set: all participants who received talimogene laherparepvec (TL) or surgical resection of melanoma tumor lesion(s).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | All TEAEs | 32 Participants |
| Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥4 | 0 Participants |
| Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered | NA Participants |
| Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥2 | 19 Participants |
| Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to Interruption of TL | NA Participants |
| Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Serious TEAEs | 2 Participants |
| Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥3 | 4 Participants |
| Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Fatal Adverse Events | 0 Participants |
| Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Nonserious | NA Participants |
| Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to DC of TL | NA Participants |
| Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Serious | NA Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to DC of TL | 1 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Serious | 1 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to Interruption of TL | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered | 1 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥3 | 1 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Fatal Adverse Events | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥4 | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Nonserious | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Serious TEAEs | 1 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥2 | 20 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | All TEAEs | 53 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Nonserious | 1 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | All TEAEs | 19 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥2 | 12 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥3 | 7 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥4 | 0 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Serious TEAEs | 8 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to DC of TL | 0 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to Interruption of TL | 0 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered | 1 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Serious | 0 Participants |
| Talimogene Laherparepvec: Post-Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Fatal Adverse Events | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to DC of TL | 3 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Fatal Adverse Events | 0 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Serious | 2 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Serious TEAEs | 13 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥4 | 1 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥3 | 11 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered: Nonserious | 1 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Grade ≥2 | 38 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | All TEAEs | 70 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to <4 ml TL Administered | 3 Participants |
| Talimogene Laherparepvec Plus Surgery | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions | Leading to Interruption of TL | 0 Participants |
Secondary
Overall Survival (Kaplan-Meier)
Overall Survival (OS) is defined as the time from randomization to the date of death due to any cause.
Time frame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Surgery | Overall Survival (Kaplan-Meier) | NA months |
| Talimogene Laherparepvec Plus Surgery | Overall Survival (Kaplan-Meier) | NA months |
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.
Time frame: 18 weeks after last participant randomized (data cutoff date of 30 April 2019)
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Surgery | Pathological Complete Response (pCR) Rate | 2.7 percentage of participants |
| Talimogene Laherparepvec Plus Surgery | Pathological Complete Response (pCR) Rate | 17.1 percentage of participants |
p-value: 0.00380% CI: [7.4, 21.6]Chi-squared
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.
Time frame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Surgery | Regional Recurrence-Free Survival (RRFS) | 0.0 months |
| Talimogene Laherparepvec Plus Surgery | Regional Recurrence-Free Survival (RRFS) | 0.0 months |
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.
Time frame: 5 years after the last participant was randomized (last subject last visit occurred 28 April 2022)
Population: Intent to Treat Analysis Set: all participants who were randomized to either treatment group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Surgery | RFS | 0.03 months |
| Talimogene Laherparepvec Plus Surgery | RFS | 0.03 months |
p-value: 0.09280% CI: [0.6, 0.97]Log Rank