Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Talimogene laherparepvec

Antineoplastic Agents, Immunological

Surgical resection of melanoma tumor lesion(s)

Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s).

Talimogene laherparepvec will be administered by intralesional injection into the injectable cutaneous, subcutaneous, and nodal tumors initially at a dose of 10\^6 plaque forming units (PFU)/mL at day 1 of week 1 followed by a dose of 10\^8 PFU/mL at day 1 (±3 days) of week 4, 6, 8, 10 and 12 or until all injectable tumors have disappeared, or intolerance of study treatment or in the opinion of the investigator, immediate surgical resection or any other treatment for melanoma is warranted, whichever occurs first.

Talimogene Laherparepvec

Surgical resection of melanoma tumor lesion(s) will be performed after randomization any time during weeks 1 to 6.

Immediate surgical resection of melanoma lesion(s)

This is a phase 2, multicenter, randomized, open-label study to estimate the efficacy of talimogene laherparepvec as a neoadjuvant treatment followed by surgery compared to surgery alone in subjects with completely resectable stage IIIB, IIIC, or IVM1a melanoma.

This is a phase 2, multicenter, randomized, open-label study to estimate the efficacy of talimogene laherparepvec as a neoadjuvant treatment followed by surgery compared to surgery alone in subjects with completely resectable stage IIIB, IIIC, or IVM1a melanoma.

Arm 1: Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s).

Arm 2: Immediate surgical resection of melanoma tumor lesion(s) Following surgery, adjuvant systemic therapy and/or radiotherapy may be administered at the investigator's discretion and per the institutional standard of care.

Subjects will be followed for safety approximately 30 (+15) days after surgery and for disease recurrence, subsequent anticancer therapy, and survival every 3 months (±30 days) for first 3 years after the end of the safety follow-up period and then every 6 months (±30 days) until death, subject withdraws full consent, or up to 5 years after the last subject is randomized.

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

A Phase 2, Multicenter, Randomized, Open-label Trial Assessing the Efficacy and Safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery Versus Surgery Alone for Resectable, Stage IIIB to IVM1a Melanoma

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Recurrence free survival (RFS) is defined as the time from randomization to the date of event, and is presented as a Kaplan Meier estimate of time to events. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without a histopathology tumor-free margin (R0) surgical outcome or those who withdrew prior to surgery were considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment.

Kaplan-Meier estimates of the percentage of participants with RFS at 1 year, 2 years, 3 years, and 5 years from randomization. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment. Rate is presented as the percentage of participants with RFS at given time point.

Histopathology tumor-free margin (R0) surgical resection is defined by pathologist as absence of ink on the tumor for all disease. Rate is presented as the percentage of participants with histopathology tumor-free margin (R0) surgical resection.

Pathological Complete Response (pCR) is defined as no evidence of viable tumor cells on complete pathological evaluation of the surgical specimen per institutional standards of care. Rate is presented as the percentage of participants with pCR.

Local recurrence-free survival (LRFS) is defined as the time from randomization to the earlier date of the first of local disease recurrence or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Local recurrence is defined as histologically or cytologically confirmed reappearance of melanoma in the area of up to 2 cm from the scar from the surgical excision or at the edge of the skin graft if that was used for closure.

Regional recurrence-free survival (RRFS) is defined as the time from randomization to the date of the first of regional disease recurrence or death due to any cause. Participants without an R0 surgical outcome or those who withdrew prior to surgery are considered an event at randomization. Regional recurrence excludes local recurrence and is defined as histologically, cytologically, or radiographically confirmed reappearance of melanoma in the regional lymph node basin.

Distant metastases-free survival (DMFS) 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.

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

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

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.

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%.

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%.

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.

Amgen

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).

Immediate surgical resection of melanoma lesion(s) any time during Weeks 1 to 6.

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 PLUS SURGERY

Talimogene Laherparepvec Plus Surgery

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Stage IIIB Nodal

Stage IIIB In-Transit

Stage IIIC Nodal

Stage IIIC In-Transit With Nodal

Stage IV M1a

The clinical participants were staged according to the American Joint Committee of Cancer (AJCC) 7th edition Melanoma Staging System, which combines tumor staging, nodal staging and metastasis to derive an overall stage. The order of prognostication is as follows: stage IIIB (better prognosis) \> stage IIIC \> stage IV M1a (worse prognosis).

Randomization was stratified by disease stage and planned adjuvant therapy (adjuvant systemic therapy with or without radiotherapy vs radiotherapy without adjuvant systemic therapy vs none).

Stratification Factor: Disease Stage

Adjuvant Systemic Therapy W/ or W/O Radiotherapy

Radiotherapy W/O Adjuvant Systemic Therapy

None

Randomization was stratified by disease stage (IIIB nodal vs IIIB in-transit vs IIIC nodal vs IIIC in-transit with nodal vs IVM1a) and planned adjuvant therapy (adjuvant systemic therapy with (W/) or without (W/O) radiotherapy vs radiotherapy without (W/O) adjuvant systemic therapy vs none).

Stratification Factor: Planned Adjuvant Therapy

Intent to Treat Analysis Set: all participants who were randomized to either treatment group.

Study Director

Recurrence-Free Survival (RFS)

RFS at 1 Year

RFS at 2 Years

RFS at 3 Years

RFS at 5 Years

Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years

Histopathology Tumor-Free Margin (R0) Surgical Resection Rate

Pathological Complete Response (pCR) Rate

Local Recurrence-Free Survival (LRFS)

Regional Recurrence-Free Survival (RRFS)

Distant Metastases-Free Survival (DMFS)

Overall Survival (Kaplan-Meier)

Year 1

Year 2

Year 3

Year 5

Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years

Best Overall Tumor Response Per Investigator Response Rate (Talimogene Laherparepvec Arm Only)

Lesion Objective Response Rate: Injected Lesions (Talimogene Laherparepvec Arm Only)

Lesion Objective Response Rate: Uninjected Lesions (Talimogene Laherparepvec Arm Only)

All TEAEs

Grade ≥2

Grade ≥3

Grade ≥4

Serious TEAEs

Leading to DC of TL

Leading to Interruption of TL

Leading to <4 ml TL Administered

Leading to <4 ml TL Administered: Serious

Leading to <4 ml TL Administered: Nonserious

Fatal Adverse Events

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: Pre-Surgery

Talimogene Laherparepvec: Post-Surgery

Safety Analysis Set: all participants who received talimogene laherparepvec (TL) or surgical resection of melanoma tumor lesion(s).

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions

Safety Analysis Set: all participants who received talimogene laherparepvec (TL).

Spots Global Cancer Trial Database for immediate surgical resection of melanoma lesion(s)