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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Treatment with IMLYGIC® in earlier stages provided the most pronounced results1

Durable Response Rate Overall Response Rate

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

Primary endpoint1,2

The primary efficacy endpoint in the OPTiM pivotal trial was Durable Response Rate (DRR).

Nearly 1/3 of durable responders had no evidence of disease for ≥ 6 months4

Durable Response Rate1,2,4,5

IMLYGIC® Durable Response Rate (DRR)

Note: Patients were staged based on the AJCC 7th edition.
CR: Disappearance of all evidence of tumor.5
PR: ≥ 50% reduction in the sum of the products of the perpendicular diameters of all measurable tumors, as compared to baseline.5

IMLYGIC® Durable Response Rate (DRR)

Durable Response Rate – substage data1,4

IMLYGIC® Durable Response Rate – substage data

IMLYGIC® Durable Response Rate – substage data


Note: Patients were staged based on the AJCC 7th edition.
CR: Disappearance of all evidence of tumor.5
PR: ≥ 50% reduction in the sum of the products of the perpendicular diameters of all measurable tumors, as compared to baseline.5

Note: Among the PR → CR group, CR was not maintained for 6 continuous months.6
†One patient disease substage was unknown.1
‡GM-CSF: CR of IIIB/C 0% (0/0), PR of IIIB/C 0% (0/0).4
§GM-CSF: CR of IVM1a 0% (0/1), PR of IVM1a 100% (1/1).4
**GM-CSF: CR of IVM1b/c 0% (0/2), PR of IVM1b/c 100% (2/2).4
CI = confidence interval; CR = Complete Response; DRR = Durable Response Rate; GM-CSF = granulocyte-macrophage colony-stimulating factor; PR = Partial Response; RR = Relative Risk.

DRR, Defined

The percent of patients with Complete Response or Partial Response maintained continuously for a minimum of 6 months.1,2

Key secondary endpoints1,2

The key secondary endpoints in the OPTiM pivotal trial were time to response, Overall Survival (OS), and Overall Response Rate (ORR).

  • The median time to response was 4.1 (range: 1.2 to 16.7) months in the IMLYGIC® arm.2
  • There was no statistically significant difference in OS between the IMLYGIC® and the GM-CSF arms. The median OS in the overall study population was 22.9 months in the IMLYGIC® arm and 19.0 months in the GM-CSF arm (P = 0.116).2

Overall Response Rate1,5

IMLYGIC® Overall Response Rate (ORR)

*GM-CSF: CR of ORR 12.5% (1/8), PR of ORR 87.5% (7/8)1
Note: Patients were staged based on the AJCC 7th edition.
CR: Disappearance of all evidence of tumor.5
PR: ≥ 50% reduction in the sum of the products of the perpendicular diameters of all measurable tumors, as compared to baseline.5

IMLYGIC® Overall Response Rate (ORR)

1 in 4 IMLYGIC® patients demonstrated a ≥ 50% reduction in tumor volume1,5

Overall Response Rate - substage data1,6

IMLYGIC® Overall Response Rate – substage data

IMLYGIC® Overall Response Rate – substage data

*GM-CSF: CR of ORR 12.5% (1/8), PR of ORR 87.5% (7/8)1
Note: Patients were staged based on the AJCC 7th edition.
CR: Disappearance of all evidence of tumor.5
PR: ≥ 50% reduction in the sum of the products of the perpendicular diameters of all measurable tumors, as compared to baseline.5

1 in 4 IMLYGIC® patients demonstrated a ≥ 50% reduction in tumor volume1,5

Important ORR considerations:

CR and PR are the components of our prespecified objective of DRR, which is defined as the percentage of patients experiencing CR or PR lasting ≥ 6 months. However, the rates of CR and/or PR were not independent, prespecified endpoints. ORR, the percentage of patients experiencing CR or PR, was also not a prespecified objective; therefore, the study was not designed to statistically assess ORR.

†One patient disease substage was unknown.1
‡GM-CSF: CR of IIIB/C 0% (0/1), PR of IIIB/C 100% (1/1).6
§GM-CSF: CR of IVM1a 0% (0/1), PR of IVM1a 100% (1/1).6
**GM-CSF: CR of IVM1b/c 16.7% (1/6), PR of IVM1b/c 83.3% (5/6).6

CR = Complete Response; DRR = Durable Response Rate; GM-CSF = granulocyte-macrophate colony-stimulating factor; ORR = Overall Response Rate; PR = Partial Response.

ORR, Defined

ORR was defined as the percentage of patients experiencing a CR or PR.1

12EfficacyDurableResponsePivotalTrialIcon12EfficacyDurableResponsePivotalTrialIcon

See the details of the OPTiM Pivotal Trial

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REFERENCES

  1. 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.
  2. IMLYGIC® (talimogene laherparepvec) Prescribing Information, BioVex, Inc., a subsidiary of Amgen Inc.
  3. 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.
  4. Data on file, Amgen; [1]; 2017.
  5. 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/JC0.2014.58.3377.
  6. Data on file, Amgen; [2]; 2017.

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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