Trial Outcomes & Findings for An Extended Use Study of Safety and Efficacy of Talimogene Laherparepvec in Melanoma (NCT NCT01368276)

Last Updated: 2015-12-18

Results Overview

AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 based on the following guideline: Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE. Treatment-related AE refers to AEs that have possible or probable relation to study treatment as determined by the investigator. A serious AE is one that meets one or more of the following criteria/outcomes: * Results in death. * Is life-threatening. * Requires inpatient hospitalization or prolongation of existing hospitalization. * Results in persistent or significant disability/incapacity. * Is a congenital anomaly/birth defect. * Is an important medical event.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

31 participants

Primary outcome timeframe

From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group.

Results posted on

2015-12-18

Participant Flow

This extension was available to patients who participated in study 005/05 (NCT00769704), received the maximum allowable number of treatments or developed new lesion(s) within ≤ 12 months from the end of treatment visit after previous resolution of all disease while on study 005/05, and warranted further treatment per the investigator.

Participants received the same treatment as randomized under the 005/05 study.

Participant milestones

Participant milestones
Measure	GM-CSF Granulocyte macrophage colony-stimulating factor (GM-CSF) was administered at a dose of 125 μg/m²/day subcutaneously for 14 consecutive days followed by 14 days of rest, in 28-day treatment cycles for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.	Talimogene Laherparepvec Talimogene laherparepvec was administered at a concentration of 10⁸ plaque forming units (PFU)/mL injected into 1 or more skin or subcutaneous tumors on Days 1 and 15 of each 28-day cycle for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.
Overall Study STARTED	3	28
Overall Study COMPLETED	2	18
Overall Study NOT COMPLETED	1	10

Reasons for withdrawal

Reasons for withdrawal
Measure	GM-CSF Granulocyte macrophage colony-stimulating factor (GM-CSF) was administered at a dose of 125 μg/m²/day subcutaneously for 14 consecutive days followed by 14 days of rest, in 28-day treatment cycles for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.	Talimogene Laherparepvec Talimogene laherparepvec was administered at a concentration of 10⁸ plaque forming units (PFU)/mL injected into 1 or more skin or subcutaneous tumors on Days 1 and 15 of each 28-day cycle for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.
Overall Study Death	1	10

Baseline Characteristics

An Extended Use Study of Safety and Efficacy of Talimogene Laherparepvec in Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GM-CSF n=3 Participants GM-CSF was administered at a dose of 125 μg/m²/day subcutaneously for 14 consecutive days followed by 14 days of rest, in 28-day treatment cycles for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.	Talimogene Laherparepvec n=28 Participants Talimogene laherparepvec was administered at a concentration of 10⁸ PFU/mL injected into 1 or more skin or subcutaneous tumors on Days 1 and 15 of each 28-day cycle for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.	Total n=31 Participants Total of all reporting groups
Age, Continuous	54.7 years STANDARD_DEVIATION 25.0 • n=5 Participants	64.2 years STANDARD_DEVIATION 13.2 • n=7 Participants	63.3 years STANDARD_DEVIATION 14.4 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	14 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	14 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized White	3 participants n=5 Participants	28 participants n=7 Participants	31 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	3 participants n=5 Participants	20 participants n=7 Participants	23 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	0 participants n=5 Participants	8 participants n=7 Participants	8 participants n=5 Participants
Disease Stage Stage IIIB	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Disease Stage Stage IIIC	0 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants
Disease Stage Stage IV M1a	1 participants n=5 Participants	9 participants n=7 Participants	10 participants n=5 Participants
Disease Stage Stage IV M1b	1 participants n=5 Participants	8 participants n=7 Participants	9 participants n=5 Participants
Disease Stage Stage IV M1c	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants

PRIMARY outcome

Timeframe: From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group.

Population: Safety population (randomized participants who received at least one dose of extension treatment).

Outcome measures

Outcome measures
Measure	GM-CSF n=3 Participants GM-CSF was administered at a dose of 125 μg/m²/day subcutaneously for 14 consecutive days followed by 14 days of rest, in 28-day treatment cycles for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.	Talimogene Laherparepvec n=28 Participants Talimogene laherparepvec was administered at a concentration of 10⁸ PFU/mL injected into 1 or more skin or subcutaneous tumors on Days 1 and 15 of each 28-day cycle for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.
Number of Participants With Treatment-emergent Adverse Events (AEs) All adverse events	3 participants	26 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Worst grade of 3	0 participants	5 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Worst grade of 4	0 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Worst grade of 5	0 participants	2 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Serious adverse events	0 participants	9 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Treatment-related adverse events	3 participants	20 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Treatment-related serious adverse events	0 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Leading to discontinuation of study treatment	0 participants	4 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Leading to study treatment delay	0 participants	4 participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Fatal adverse events on-study	0 participants	2 participants

SECONDARY outcome

Timeframe: From randomization in study 005/05 until the data-cut-off date for the extension period of 08 August 2014; median treatment duration for 005/05 and 005/05-E studies combined was 88 weeks for talimogene laherparepvec and 100 weeks for GM-CSF.

Population: The full analysis set for the extension study is defined as all participants who received at least one dose of extension treatment.

Objective response rate was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) assessed by the investigator. Best overall response for a patient is the best overall response observed across all time points and is cumulative (ie, includes responses during the parent study 005/05 and during Study 005/05-E). Disease assessments were performed at the beginning of each treatment cycle and assessed in accordance with modified World Health Organization criteria. CR: Disappearance of all clinical evidence of tumor (both measurable and non-measurable but evaluable disease); 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 baseline.

Outcome measures

Outcome measures
Measure	GM-CSF n=3 Participants GM-CSF was administered at a dose of 125 μg/m²/day subcutaneously for 14 consecutive days followed by 14 days of rest, in 28-day treatment cycles for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.	Talimogene Laherparepvec n=28 Participants Talimogene laherparepvec was administered at a concentration of 10⁸ PFU/mL injected into 1 or more skin or subcutaneous tumors on Days 1 and 15 of each 28-day cycle for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.
Objective Response Rate	100.0 percentage of participants For 100% response, the asymptotic 95% CI was not estimated since the mathematical formula is not considered appropriate in such extreme cases.	57.1 percentage of participants Interval 38.8 to 75.5

SECONDARY outcome

Population: Full analysis set

Durable response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) assessed by the investigator, initiating at any time while receiving talimogene laherparepvec or GM-CSF therapy on the 005/05 or the 005/05-E study and maintained continuously for at least 6 months from response initiation. This reflects all new sites of disease as well as disease sites identified at baseline. Disease assessments were performed at the beginning of each treatment cycle in accordance with modified World Health Organization criteria. CR: Disappearance of all clinical evidence of tumor (both measurable and non-measurable but evaluable disease); 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 baseline.

Outcome measures

Outcome measures
Measure	GM-CSF n=3 Participants GM-CSF was administered at a dose of 125 μg/m²/day subcutaneously for 14 consecutive days followed by 14 days of rest, in 28-day treatment cycles for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.	Talimogene Laherparepvec n=28 Participants Talimogene laherparepvec was administered at a concentration of 10⁸ PFU/mL injected into 1 or more skin or subcutaneous tumors on Days 1 and 15 of each 28-day cycle for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.
Durable Response Rate	33.3 percentage of participants Interval 0.0 to 86.7	32.1 percentage of participants Interval 14.8 to 49.4

Adverse Events

GM-CSF

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Talimogene Laherparepvec

Serious events: 9 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GM-CSF n=3 participants at risk GM-CSF was administered at a dose of 125 μg/m²/day subcutaneously for 14 consecutive days followed by 14 days of rest, in 28-day treatment cycles for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.	Talimogene Laherparepvec n=28 participants at risk Talimogene laherparepvec was administered at a concentration of 10⁸ PFU/mL injected into 1 or more skin or subcutaneous tumors on Days 1 and 15 of each 28-day cycle for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met.
Cardiac disorders Cardiac arrest	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Restrictive cardiomyopathy	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Disease progression	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of liver	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic malignant melanoma	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal failure	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypovolaemic shock	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Vasculitis	0.00% 0/3 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 1/28 • From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Additional Information

Study Director

Amgen, Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER