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