Trial Outcomes & Findings for Efficacy and Safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery Versus Surgery Alone for Melanoma (NCT NCT02211131)

NCT ID: NCT02211131

Last Updated: 2023-06-05

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 150 participants
• Primary outcome timeframe: 24 months after last participant was randomized (data cutoff date of 30 April 2019)
• Results posted on: 2023-06-05

Participant Flow

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.

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.

Participant milestones

Measure	Surgery Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	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.
Overall Study STARTED	74	76
Overall Study COMPLETED	40	48
Overall Study NOT COMPLETED	34	28

Reasons for withdrawal

Measure	Surgery Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	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.
Overall Study Death	26	16
Overall Study Lost to Follow-up	4	3
Overall Study Decision by Sponsor	1	1
Overall Study Withdrawal by Subject	3	8

Baseline Characteristics

Efficacy and Safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery Versus Surgery Alone for Melanoma

Baseline characteristics by cohort

Measure	Surgery n=74 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=76 Participants 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.	Total n=150 Participants Total of all reporting groups
Age, Continuous	59.1 years STANDARD_DEVIATION 16.1 • n=5 Participants	62.6 years STANDARD_DEVIATION 12.6 • n=7 Participants	60.9 years STANDARD_DEVIATION 14.5 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	49 Participants n=7 Participants	96 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	69 Participants n=5 Participants	70 Participants n=7 Participants	139 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	73 Participants n=5 Participants	73 Participants n=7 Participants	146 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Stratification Factor: Disease Stage Stage IIIB Nodal	14 participants n=5 Participants	15 participants n=7 Participants	29 participants n=5 Participants
Stratification Factor: Disease Stage Stage IIIB In-Transit	17 participants n=5 Participants	16 participants n=7 Participants	33 participants n=5 Participants
Stratification Factor: Disease Stage Stage IIIC Nodal	14 participants n=5 Participants	13 participants n=7 Participants	27 participants n=5 Participants
Stratification Factor: Disease Stage Stage IIIC In-Transit With Nodal	17 participants n=5 Participants	17 participants n=7 Participants	34 participants n=5 Participants
Stratification Factor: Disease Stage Stage IV M1a	12 participants n=5 Participants	15 participants n=7 Participants	27 participants n=5 Participants
Stratification Factor: Planned Adjuvant Therapy Adjuvant Systemic Therapy W/ or W/O Radiotherapy	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants
Stratification Factor: Planned Adjuvant Therapy Radiotherapy W/O Adjuvant Systemic Therapy	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Stratification Factor: Planned Adjuvant Therapy None	62 participants n=5 Participants	64 participants n=7 Participants	126 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Surgery n=74 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=76 Participants 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.	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.	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.
Recurrence-Free Survival (RFS)	0.0 months NA=not estimable. There are not enough events to estimate a standard error for the median survival time, confidence intervals (CIs) are not estimable.	0.0 months Interval 0.0 to 6.5	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Surgery n=74 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=76 Participants 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.	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.	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.
RFS	0.03 months NA=not estimable. There are not enough events to estimate a standard error for the median survival time, confidence intervals (CIs) are not estimable.	0.03 months Interval 0.03 to 6.54	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Surgery n=74 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=76 Participants 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.	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.	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.
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 Interval 15.88 to 28.65	33.73 percentage of participants Interval 26.82 to 40.76	—	—
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 Interval 10.01 to 21.38	22.32 percentage of participants Interval 16.39 to 28.84	—	—
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 Interval 11.44 to 23.23	29.51 percentage of participants Interval 22.91 to 36.4	—	—
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 Interval 11.44 to 23.23	28.11 percentage of participants Interval 21.62 to 36.94	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Surgery n=74 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=76 Participants 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.	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.	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.
Histopathology Tumor-Free Margin (R0) Surgical Resection Rate	37.8 percentage of participants Interval 30.3 to 45.9	42.1 percentage of participants Interval 34.4 to 50.1	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Surgery n=74 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=76 Participants 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.	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.	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.
Pathological Complete Response (pCR) Rate	2.7 percentage of participants Interval 0.7 to 7.0	17.1 percentage of participants Interval 11.6 to 24.0	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Surgery n=74 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=76 Participants 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.	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.	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.
Local Recurrence-Free Survival (LRFS)	0.0 months NA=not estimable. There are not enough events to estimate a standard error for the median survival time, confidence intervals are not estimable.	0.0 months Interval 0.0 to 7.1	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Surgery n=74 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=76 Participants 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.	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.	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.
Regional Recurrence-Free Survival (RRFS)	0.0 months NA=not estimable. There are not enough events to estimate a standard error for the median survival time, confidence intervals are not estimable.	0.0 months Interval 0.0 to 12.9	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Surgery n=74 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=76 Participants 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.	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.	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.
Distant Metastases-Free Survival (DMFS)	0.0 months NA = not estimable. There are not enough events to estimate a standard error for the median survival time, confidence intervals are not estimable.	0.0 months Interval 0.0 to 6.5	—	—

SECONDARY outcome

Timeframe: 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.

Overall Survival (OS) is defined as the time from randomization to the date of death due to any cause.

Outcome measures

Measure	Surgery n=74 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=76 Participants 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.	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.	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.
Overall Survival (Kaplan-Meier)	NA months NA=not estimable. Not enough events occurred to estimate the median and the confidence intervals.	NA months NA=not estimable. There are not enough events to estimate a standard error for the median survival time, confidence interval is not estimable.	—	—

SECONDARY outcome

Timeframe: 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.

Kaplan-Meier estimates of the percentage of participants alive at 1 year, 2 years, 3 years, and 5 years from randomization.

Outcome measures

Measure	Surgery n=74 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=76 Participants 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.	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.	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.
Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years Year 1	85.92 percentage of participants Interval 79.63 to 90.38	95.89 percentage of participants Interval 91.58 to 98.02	—	—
Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years Year 2	77.44 percentage of participants Interval 70.29 to 83.08	88.94 percentage of participants Interval 83.16 to 92.82	—	—
Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years Year 3	71.59 percentage of participants Interval 64.03 to 77.84	83.27 percentage of participants Interval 76.7 to 88.13	—	—
Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years Year 5	62.29 percentage of participants Interval 54.75 to 69.62	77.32 percentage of participants Interval 70.12 to 83.0	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Surgery n=76 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	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.	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.	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.
Best Overall Tumor Response Per Investigator Response Rate (Talimogene Laherparepvec Arm Only)	13.2 percentage of participants Interval 8.3 to 19.5	—	—	—

SECONDARY outcome

Timeframe: 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.

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%.

Outcome measures

Measure	Surgery n=76 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	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.	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.	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.
Lesion Objective Response Rate: Injected Lesions (Talimogene Laherparepvec Arm Only)	26.3 percentage of lesions Interval 19.7 to 33.9	—	—	—

SECONDARY outcome

Timeframe: 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.

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%.

Outcome measures

Measure	Surgery n=76 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	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.	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.	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.
Lesion Objective Response Rate: Uninjected Lesions (Talimogene Laherparepvec Arm Only)	3.9 percentage of lesions Interval 1.5 to 8.6	—	—	—

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Measure	Surgery n=69 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=57 Participants 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.	Talimogene Laherparepvec: Post-Surgery n=57 Participants 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.	Talimogene Laherparepvec Plus Surgery n=73 Participants 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.
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	53 Participants	19 Participants	70 Participants
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	20 Participants	12 Participants	38 Participants
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	1 Participants	7 Participants	11 Participants
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	0 Participants	0 Participants	1 Participants
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	1 Participants	8 Participants	13 Participants
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 no TL administered	1 Participants	0 Participants	3 Participants
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 no TL administered	0 Participants	0 Participants	0 Participants
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 no TL administered	1 Participants	1 Participants	3 Participants
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 no TL administered	1 Participants	0 Participants	2 Participants
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 no TL administered	0 Participants	1 Participants	1 Participants
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	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Measure	Surgery n=57 Participants Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	Talimogene Laherparepvec Plus Surgery n=57 Participants 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.	Talimogene Laherparepvec: Post-Surgery n=73 Participants 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.	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.
Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions All TEAEs	51 Participants	0 Participants	64 Participants	—
Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions Grade ≥2	13 Participants	0 Participants	20 Participants	—
Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions Grade ≥3	1 Participants	0 Participants	3 Participants	—
Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions Grade ≥4	0 Participants	0 Participants	0 Participants	—
Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions Serious TEAEs	1 Participants	0 Participants	2 Participants	—
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	0 Participants	1 Participants	—
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	0 Participants	0 Participants	—
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	0 Participants	1 Participants	—
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	0 Participants	1 Participants	—
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	0 Participants	0 Participants	—
Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions Fatal Adverse Events	0 Participants	0 Participants	0 Participants	—

Adverse Events

Surgery

Serious events: 2 serious events

Other events: 14 other events

Deaths: 26 deaths

TALIMOGENE LAHERPAREPVEC PLUS SURGERY

Serious events: 13 serious events

Other events: 62 other events

Deaths: 16 deaths

Serious adverse events

Measure	Surgery n=69 participants at risk Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	TALIMOGENE LAHERPAREPVEC PLUS SURGERY n=73 participants at risk 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.
Gastrointestinal disorders Nausea	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/69 • 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).	1.4% 1/73 • 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).
General disorders Asthenia	0.00% 0/69 • 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).	1.4% 1/73 • 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).
General disorders Pain	0.00% 0/69 • 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).	1.4% 1/73 • 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).
General disorders Pyrexia	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Hepatobiliary disorders Cholecystitis	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Infections and infestations Cellulitis	0.00% 0/69 • 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).	2.7% 2/73 • 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).
Infections and infestations Influenza	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Infections and infestations Postoperative wound infection	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Infections and infestations Urinary tract infection	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Infections and infestations Wound abscess	1.4% 1/69 • 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).	0.00% 0/73 • 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).
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Nervous system disorders Cerebral ischaemia	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Pregnancy, puerperium and perinatal conditions Anembryonic gestation	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Product Issues Device occlusion	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Surgical and medical procedures Neck dissection	0.00% 0/69 • 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).	1.4% 1/73 • 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).
Vascular disorders Peripheral embolism	1.4% 1/69 • 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).	0.00% 0/73 • 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).

Other adverse events

Measure	Surgery n=69 participants at risk Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.	TALIMOGENE LAHERPAREPVEC PLUS SURGERY n=73 participants at risk 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.
Gastrointestinal disorders Diarrhoea	0.00% 0/69 • 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).	11.0% 8/73 • 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).
Gastrointestinal disorders Nausea	1.4% 1/69 • 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).	9.6% 7/73 • 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).
Gastrointestinal disorders Vomiting	0.00% 0/69 • 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).	9.6% 7/73 • 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).
General disorders Chills	0.00% 0/69 • 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).	24.7% 18/73 • 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).
General disorders Fatigue	1.4% 1/69 • 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).	27.4% 20/73 • 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).
General disorders Influenza like illness	0.00% 0/69 • 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).	35.6% 26/73 • 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).
General disorders Injection site erythema	0.00% 0/69 • 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).	5.5% 4/73 • 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).
General disorders Injection site pain	0.00% 0/69 • 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).	8.2% 6/73 • 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).
General disorders Injection site reaction	0.00% 0/69 • 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).	5.5% 4/73 • 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).
General disorders Pain	8.7% 6/69 • 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).	6.8% 5/73 • 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).
General disorders Pyrexia	2.9% 2/69 • 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).	32.9% 24/73 • 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).
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/69 • 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).	13.7% 10/73 • 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).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/69 • 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).	11.0% 8/73 • 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).
Musculoskeletal and connective tissue disorders Pain in extremity	5.8% 4/69 • 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).	1.4% 1/73 • 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).
Nervous system disorders Dizziness	0.00% 0/69 • 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).	9.6% 7/73 • 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).
Nervous system disorders Headache	0.00% 0/69 • 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).	23.3% 17/73 • 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).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/69 • 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).	5.5% 4/73 • 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).
Skin and subcutaneous tissue disorders Pruritus	1.4% 1/69 • 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).	5.5% 4/73 • 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).

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: medinfo@amgen.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER