INDICATION & 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...READ MORE

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Introducing OPTiM

Oncovex (GM-CSF) Pivotal Trial in Melanoma

Study design

Oncovex (GM-CSF) Pivotal Trial in Melanoma (OPTiM) was a phase 3, multicenter, open-label study of 436 stage IIIB, IIIC, and IV patients (previously treated and untreated). Patients had injectable, unresectable melanoma and were randomized 2:1 to receive IMLYGIC® or GM-CSF.1,2,3

A total of 436 patients were randomized to receive either IMLYGIC® (talimogene laherparepvec) (n = 295) or GM-CSF (n = 141).1

INJECTABLE, UNRESECTABLE

Stage IIIB, IIIC, and IV melanoma1 (N = 436)

RANDOMIZED 2:11,3

IMLYGIC® intralesional injection (n = 295)
GM-CSF subcutaneous injection (n = 141)

Patients were to be treated for a minimum of 6 months unless other treatment was required 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

Eligibility criteria

Inclusion/exclusion criteria

Patient characteristics employed in the phase 3 clinical trial are the following1-4:

Key Inclusion
Criteria
  • Adults aged ≥ 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
  • Patients requiring intermittent or chronic treatment with an antiviral agent or high-dose steroids

Select baseline characteristics

Select baseline demographics and clinical characteristics3

Chart of baseline characteristics of patients

Chart of baseline characteristics of patients

Endpoints

Primary endpoint1

The major efficacy outcome in the trial was durable response rate (DRR).

  • DRR: defined as the percent of patients with a CR or PR maintained continuously for a minimum of 6 months1,*
    • CR: disappearance of all evidence of tumor3
    • PR: ≥ 50% reduction in the sum of the products of the perpendicular diameters of all measurable tumors at the time of assessment, as compared to baseline3

*Tumor responses determined using modified World Health Organization (WHO) criteria by a blinded, independent Endpoint Assessment Committee (EAC).3,4

IMLYGIC® was injected into cutaneous, subcutaneous, or nodal melanoma lesions and was not injected into visceral lesions.

Secondary endpoints1

Key secondary endpoints3:

  • Median Time to Response
    • The median time to response was 4.1 months (range: 1.2 to 16.7 months) in the IMLYGIC® arm1
  • Overall Survival
    • There was no statistically significant difference in overall survival between the IMLYGIC® and the GM-CSF arms1
11EfficacyOPTiMPivotalTrialTargetedResponseIcon11EfficacyOPTiMPivotalTrialTargetedResponseIcon

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REFERENCES

  1. IMLYGIC® (talimogene laherparepvec) Prescribing Information, BioVex, Inc., a subsidiary of Amgen Inc.
  2. Kaufman HL, Bines SD. OPTiM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma. Future Oncol. 2010;6:941-949.
  3. Andtbacka RHI, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33:2780-2788.
  4. Andtbacka RHI, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33(suppl Clinical Study Protocol):doi:10.1200/JCO.2014.58.3377.

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 but not limited to cold sores and herpetic keratitis) and serious cases of disseminated herpetic infections have been reported in IMLYGIC-® treated patients, including fatal disseminated herpetic infection in the immunocompromised patient population. Immunocompromised patients may be at increased risk of life-threatening disseminated herpetic infection. 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 the 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.
  • Obstructive Airway Disorder: Obstructive airway disorder has been reported following IMLYGIC® treatment. Use caution when injecting lesions close to major airways.
  • Hepatic Hemorrhage from Transcutaneous Intrahepatic Route of Administration: IMLYGIC is not indicated for transcutaneous intrahepatic route of administration. In clinical studies, cases of hepatic hemorrhage resulting in hospitalization and death have been reported in patients receiving transcutaneous intrahepatic IMLYGIC injections
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

IMLYGIC® 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

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