Indication and Limitations of Use


IMLYGIC® (talimogene laherparepvec) is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.

Limitations of use: IMLYGIC® has not been shown to improve overall survival or have an effect on visceral metastases. Close Read More
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IMLYGIC® Efficacy

In a phase 3, multicenter, open-label, randomized clinical study, the safety and efficacy of intralesional injections of IMLYGIC® (talimogene laherparepvec) were compared with subcutaneously administered granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with stage IIIB, IIIC, and IV melanoma that was considered to be not surgically resectable.1,2 IMLYGIC® was injected into cutaneous, subcutaneous, or nodal melanoma lesions and was not injected into visceral lesions.1 Previous systemic treatment for melanoma was allowed.

Inclusion/Exclusion Criteria

Patient characteristics employed in the phase 3 clinical trial are the following1,2:

Key Inclusion Criteria

  • Adults ages ≥ 18 years
  • Previously treated and untreated not surgically resectable stage IIIB, IIIC, or IV disease 
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 
  • Injectable disease (ie, suitable for direct injection or through the use of ultrasound guidance) 
  • Serum lactate dehydrogenase (LDH) levels ≤ 1.5 × upper limit of normal (ULN)
  • At least 1 melanoma lesion ≥ 10 mm in diameter or lesions that in aggregate had a total diameter of ≥ 10 mm

Key Exclusion Criteria

  • Clinically active cerebral or any bone metastases 
  • More than 3 visceral metastases (not including lung metastases or nodal metastases associated with visceral organs) 
  • Primary ocular or mucosal melanoma 
  • Evidence of immunosuppression 
  • Open herpetic skin lesions or use of chronic anti-herpetic agents 
  • Patients requiring intermittent or chronic treatment with an antiviral agent or high-dose steroids 

Select Baseline Characteristics

See the table below for the baseline demographics of the patients included in the phase 3 clinical trial.

Phase 3 Clinical Trials Select Baseline Characteristics

Study Design

A total of 436 patients were randomized to receive either IMLYGIC® (n = 295) or GM-CSF (n = 141). IMLYGIC® was administered by intralesional injection at an initial concentration of 106 (1 million) PFU per mL on Day 1, followed by a concentration of 108 (100 million) PFU per mL on Day 21 and every 2 weeks thereafter, at a dose of up to 4 mL per visit. GM-CSF was administered subcutaneously in 28-day cycles, ie, 125 µg/m2 daily for 14 days followed by 14 days without GM-CSF administration.1

Patients were to be treated for a minimum of 6 months or until no injectable lesions were remaining. During this period, treatment could continue despite an increase in size in existing lesion(s) and/or development of new lesion(s), unless the patient developed intolerable toxicity or the investigator believed that it was in the best interest of the patient to stop treatment or to be given other therapy for melanoma.1

After 6 months of treatment, patients were to continue treatment until clinically relevant disease progression (ie, disease progression associated with a decline in performance status and/or alternative therapy was required in the opinion of the investigator), up to 12 months. Patients experiencing a response at 12 months after the start of treatment could continue treatment for up to an additional 6 months, unless there were no remaining injectable lesions or disease progression. All patients were to be followed for survival status for at least 36 months.1

Primary Endpoint: Durable Response Rate (DRR) 

The major efficacy outcome in the trial was durable response rate, defined as the percent of patients with complete response or partial response maintained continuously for a minimum of 6 months.1

  • Complete response (CR) was defined as disappearance of all evidence of tumor.3
  • Partial response (PR) was defined as a ≥ 50% reduction in the sum of the products of the perpendicular diameters of all measurable tumors at the time of assessment, as compared with baseline.3

Tumor responses were determined according to World Health Organization (WHO) response criteria modified to allow patients who developed new lesions or disease progression of existing lesions to continue the treatment and be evaluated later for tumor response.1

Durable Response Rate

Secondary Endpoints: Time to Response and Overall Survival

Key secondary endpoints included time to response and overall survival (time from random assignment to death).2

  • Median Time to Response
    • The median time to response was 4.1 months (range: 1.2 to 16.7 months) in the IMLYGIC® arm.1
  • Overall Survival
    • There was no statistically significant difference in overall survival between the IMLYGIC® and the GM-CSF arms.1

Amgen MedInfo

To report adverse events related to IMLYGIC® use, submit an inquiry, or contact a Medical Information Healthcare Professional, please call 1-800-77-AMGEN (1-800-772-6436) or visit Amgen MedInfo.

See the Product Fact Sheet for a quick view of key information, including how to order IMLYGIC® and storage and handling needs.

GET THE FACT SHEET >

Review safety information from the IMLYGIC® clinical trial in the next section.

SAFETY >
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IMLYGIC® (talimogene laherparepvec) Suspension for Injection

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IMPORTANT SAFETY INFORMATION

Contraindications
  • Do not administer IMLYGIC® to immunocompromised patients, including those with a history of primary or acquired immunodeficient states, leukemia, lymphoma, AIDS or other clinical manifestations of infection with human immunodeficiency viruses, and those on immunosuppressive therapy, due to the risk of life-threatening disseminated herpetic infection.
  • Do not administer IMLYGIC® to pregnant patients.
Warnings and Precautions
  • Accidental exposure to IMLYGIC® may lead to transmission of IMLYGIC® and herpetic infection, including during preparation and administration. Health care providers, close contacts, pregnant women, and newborns should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. The affected area in exposed individuals should be cleaned thoroughly with soap and water and/or a disinfectant.
  • Caregivers should wear protective gloves when assisting patients in applying or changing occlusive dressings and observe safety precautions for disposal of used dressings, gloves, and cleaning materials. Exposed individuals should clean the affected area thoroughly with soap and water and/or a disinfectant.
  • To prevent possible inadvertent transfer of IMLYGIC® to other areas of the body, patients should be advised to avoid touching or scratching injection sites or occlusive dressings.
  • Herpetic infections: Herpetic infections (including cold sores and herpetic keratitis) have been reported in IMLYGIC®-treated patients. Disseminated herpetic infection may also occur in immunocompromised patients. Patients who develop suspicious herpes-like lesions should follow standard hygienic practices to prevent viral transmission.
  • Patients or close contacts with suspected signs or symptoms of a herpetic infection should contact their health care provider to evaluate the lesions. Suspected herpetic lesions should be reported to Amgen at 1-855-IMLYGIC (1-855-465-9442). Patients or close contacts have the option of follow-up testing for further characterization of the infection.
  • IMLYGIC® is sensitive to acyclovir. Acyclovir or other antiviral agents may interfere with the effectiveness of IMLYGIC®. Consider the risks and benefits of IMLYGIC® treatment before administering antiviral agents to manage herpetic infection.
  • Injection Site Complications: Necrosis or ulceration of tumor tissue may occur during IMLYGIC® treatment. Cellulitis and systemic bacterial infection have been reported in clinical studies. Careful wound care and infection precautions are recommended, particularly if tissue necrosis results in open wounds.
  • Impaired healing at the injection site has been reported. IMLYGIC® may increase the risk of impaired healing in patients with underlying risk factors (eg, previous radiation at the injection site or lesions in poorly vascularized areas). If there is persistent infection or delayed healing of the injection site, consider the risks and benefits of continuing treatment.
  • Immune-Mediated events including glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis, and vitiligo have been reported in patients treated with IMLYGIC®. Consider the risks and benefits of IMLYGIC® before initiating treatment in patients who have underlying autoimmune disease or before continuing treatment in patients who develop immune-mediated events.
  • Plasmacytoma at Injection Site: Plasmacytoma in proximity to the injection site has been reported in a patient with smoldering multiple myeloma after IMLYGIC® administration in a clinical study. Consider the risks and benefits of IMLYGIC® in patients with multiple myeloma or in whom plasmacytoma develops during treatment.
Adverse Reactions
  • The most commonly reported adverse drug reactions (≥ 25%) in IMLYGIC®-treated patients were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain. Pyrexia, chills, and influenza-like illness can occur at any time during IMLYGIC® treatment, but were more frequent during the first 3 months of treatment.
  • The most common Grade 3 or higher adverse reaction was cellulitis.

Please see full Prescribing Information and Medication Guide for IMLYGIC®.

INDICATION AND LIMITATIONS OF USE

IMLYGIC® (talimogene laherparepvec) is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.

Limitations of use: IMLYGIC® has not been shown to improve overall survival or have an effect on visceral metastases.

IMPORTANT SAFETY INFORMATION

Contraindications
  • Do not administer IMLYGIC® to immunocompromised patients, including those with a history of primary or acquired immunodeficient states, leukemia, lymphoma, AIDS or other clinical manifestations of infection with human immunodeficiency viruses, and those on immunosuppressive therapy, due to the risk of life-threatening disseminated herpetic infection.
  • Do not administer IMLYGIC® to pregnant patients.
Warnings and Precautions
  • Accidental exposure to IMLYGIC® may lead to transmission of IMLYGIC® and herpetic infection, including during preparation and administration. Health care providers, close contacts, pregnant women, and newborns should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. The affected area in exposed individuals should be cleaned thoroughly with soap and water and/or a disinfectant.
  • Caregivers should wear protective gloves when assisting patients in applying or changing occlusive dressings and observe safety precautions for disposal of used dressings, gloves, and cleaning materials. Exposed individuals should clean the affected area thoroughly with soap and water and/or a disinfectant.
  • To prevent possible inadvertent transfer of IMLYGIC® to other areas of the body, patients should be advised to avoid touching or scratching injection sites or occlusive dressings.
  • Herpetic infections: Herpetic infections (including cold sores and herpetic keratitis) have been reported in IMLYGIC®-treated patients. Disseminated herpetic infection may also occur in immunocompromised patients. Patients who develop suspicious herpes-like lesions should follow standard hygienic practices to prevent viral transmission.
  • Patients or close contacts with suspected signs or symptoms of a herpetic infection should contact their health care provider to evaluate the lesions. Suspected herpetic lesions should be reported to Amgen at 1-855-IMLYGIC (1-855-465-9442). Patients or close contacts have the option of follow-up testing for further characterization of the infection.
  • IMLYGIC® is sensitive to acyclovir. Acyclovir or other antiviral agents may interfere with the effectiveness of IMLYGIC®. Consider the risks and benefits of IMLYGIC® treatment before administering antiviral agents to manage herpetic infection.
  • Injection Site Complications: Necrosis or ulceration of tumor tissue may occur during IMLYGIC® treatment. Cellulitis and systemic bacterial infection have been reported in clinical studies. Careful wound care and infection precautions are recommended, particularly if tissue necrosis results in open wounds.
  • Impaired healing at the injection site has been reported. IMLYGIC® may increase the risk of impaired healing in patients with underlying risk factors (eg, previous radiation at the injection site or lesions in poorly vascularized areas). If there is persistent infection or delayed healing of the injection site, consider the risks and benefits of continuing treatment.
  • Immune-Mediated events including glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis, and vitiligo have been reported in patients treated with IMLYGIC®. Consider the risks and benefits of IMLYGIC® before initiating treatment in patients who have underlying autoimmune disease or before continuing treatment in patients who develop immune-mediated events.
  • Plasmacytoma at Injection Site: Plasmacytoma in proximity to the injection site has been reported in a patient with smoldering multiple myeloma after IMLYGIC® administration in a clinical study. Consider the risks and benefits of IMLYGIC® in patients with multiple myeloma or in whom plasmacytoma develops during treatment.
Adverse Reactions
  • The most commonly reported adverse drug reactions (≥ 25%) in IMLYGIC®-treated patients were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain. Pyrexia, chills, and influenza-like illness can occur at any time during IMLYGIC® treatment, but were more frequent during the first 3 months of treatment.
  • The most common Grade 3 or higher adverse reaction was cellulitis.

Please see full Prescribing Information and Medication Guide for IMLYGIC®.

INDICATION AND LIMITATIONS OF USE

IMLYGIC® (talimogene laherparepvec) is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.

Limitations of use: IMLYGIC® has not been shown to improve overall survival or have an effect on visceral metastases.

References

  1. IMLYGIC® (talimogene laherparepvec) Prescribing Information, BioVex, Inc., a subsidiary of Amgen Inc.
  2. Andtbacka RHI, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33(25):2780-2788. Published online: May 26, 2015 (doi: 10.1200/JCO.2014.58.3377).
  3. Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412-7420.
  4. Data on file, Amgen Inc.