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NCT00769704 · CITED IN SOURCE DOCUMENTS

Efficacy and Safety Study of Talimogene Laherparepvec Compared to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in Melanoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2016-07-13

The objective of this study is to evaluate the efficacy and safety of treatment with talimogene laherparepvec compared to subcutaneously administered GM-CSF in patients with unresectable Stage IIIb, IIIc and Stage IV melanoma. The efficacy endpoints of the study aim to demonstrate overall clinical benefit for patients treated with talimogene laherparepvec as compared to GM-CSF.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Durable Response Rate

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outcome · POSTED

Overall Survival

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outcome · POSTED

Objective Response Rate

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outcome · POSTED

Duration of Response

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outcome · POSTED

Response Onset

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outcome · POSTED

Time to Treatment Failure

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outcome · POSTED

Response Interval

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * Males or females age ≥ 18 years * Stage IIIb, IIIc or stage IV disease that is not surgically resectable * Injectable disease (i.e. suitable for direct injection or through the use of ultrasound guidance) * At least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion \>= 10 mm in longest diameter or, multiple injectable melanoma lesions which in aggregate have a longest diameter of \>= 10 mm * Serum lactate dehydrogenase (LDH) levels less than 1.5 x upper limit of normal (ULN) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Prolongation in International Normalized Ratio (INR), Prothrombin Time (PT), and Partial Thromboplastin Time (PTT) when the result is from therapeutic anticoagulation treatment are permitted for patients whose injectable lesions are cutaneous and/or subcutaneous such that direct pressure could be applied in the event of excessive bleeding Exclusion Criteria: * Clinically active cerebral or any bone metastases. Patients with up to 3 (neurological performance status of 0) cerebral metastases may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, gammaknife therapy, with no evidence of progression, and have not required steroids, for at least two (2) months prior to randomization * Greater than 3 visceral metastases (this does not include lung metastases or nodal metastases associated with visceral organs). For patients with \< 3 visceral metastases, no lesion \> 3 cm, and liver lesions must meet Response Evaluation Criteria In Solid Tumors (RECIST) criteria for stable disease for at least 1 month prior to randomization
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Granulocyte macrophage colony-stimulating factor (GM-CSF) was administered at a dose of 125 μg/m²/day subcutaneously for 14 days, followed by a 14-day rest period for 24 weeks. Participants could continue treatment until clinically relevant disease progression, intolerability, withdrawal of consent, complete remission, or lack of response by 12 months, for a maximum of 18 months.
    intervention Names
    1. Biological: GM-CSF
    label
    GM-CSF
    type
    ACTIVE_COMPARATOR
  2. description
    Participants received talimogene laherparepvec on Days 1 and 15 of each 28-day cycle for 24 weeks. The initial dose of talimogene laherparepvec was at a concentration of 10⁶ plaque forming units (PFU)/mL, injected into 1 or more skin, subcutaneous or nodal tumors. Subsequent doses began at least 3 weeks after the first dose and consisted of talimogene laherparepvec at a concentration of 10⁸ PFU/mL. Participants could continue treatment until clinically relevant disease progression, intolerability, withdrawal of consent, complete remission, lack of response by 12 months, or disappearance of all injectable lesions, for a maximum of 18 months.
    intervention Names
    1. Biological: Talimogene laherparepvec
    label
    Talimogene Laherparepvec
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Talimogene Laherparepvec
    description
    Up to 4 mL of 10⁸ pfu/mL/per intratumoral injection
    name
    Talimogene laherparepvec
    other Names
    1. OncoVEX^GM-CSF
    2. IMLYGIC™
    type
    BIOLOGICAL
  2. arm Group Labels
    1. GM-CSF
    description
    125 µg/m² subcutaneous injection
    name
    GM-CSF
    other Names
    1. Leukine
    2. Sargramostim
    type
    BIOLOGICAL
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
437
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Durable response rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) maintained continuously for at least 6 months from the time the objective response was first observed and initiating within 12 months of starting therapy as assessed by the Endpoint Assessment Committee (EAC). 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.
    measure
    Durable Response Rate
    time Frame
    From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
secondary Outcomes
  1. description
    Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival time was censored at the last date the patient was known to be alive when the confirmation of death was absent or unknown. Participants were censored at the date of randomization if no additional follow-up data were obtained.
    measure
    Overall Survival
    time Frame
    From randomization until the first 290 survival events had occurred (data cut-off date of 31 March 2014); median time on follow-up was 44 months.
  2. description
    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 Endpoint Assessment Committee (EAC). Best overall response for a patient is the best overall response observed across all time points. 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.
    measure
    Objective Response Rate
    time Frame
    From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
  3. description
    The duration of response is defined as the longest individual period from entering response (CR or PR as assessed by the EAC) to the first documented evidence of the patient no longer meeting the criteria for being in response or death, whichever is earlier. Responses were censored at the last assessment showing response.
    measure
    Duration of Response
    time Frame
    From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
  4. description
    Response onset is defined as the time from the date of randomization to the date of the first documented evidence of response (CR or PR) per EAC assessment.
    measure
    Response Onset
    time Frame
    From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
  5. description
    Time to treatment failure was assessed by the investigator, and calculated from randomization until the first clinically relevant disease progression where there is no response achieved after the progression, or until death if no such progression occurs. Participants who did not have clinically relevant progression or did not die were censored at the time of the their last tumor assessment. Participants who withdrew from treatment due to a clinically unacceptable toxicity were not considered as an event in the analysis. Progressive disease (PD) is defined as a ≥ 25% increase in the sum of the products of the perpendicular diameters of all measurable tumors since baseline, or the unequivocal appearance of a new tumor since the last response assessment time point. Clinically relevant progressive disease is PD that is associated with a decline in performance status and/or in the opinion of the investigator the patient requires alternative therapy.
    measure
    Time to Treatment Failure
    time Frame
    From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
  6. description
    Response interval is defined as the interval between the date of randomization and the date of the last documented evidence of response (CR or PR as assessed by the Investigator) prior to any new anti-cancer therapy. Response Interval post response onset was censored if a patient was still in response at the last observation.
    measure
    Response Interval
    time Frame
    From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
Full study description
brief Summary
The objective of this study is to evaluate the efficacy and safety of treatment with talimogene laherparepvec compared to subcutaneously administered GM-CSF in patients with unresectable Stage IIIb, IIIc and Stage IV melanoma. The efficacy endpoints of the study aim to demonstrate overall clinical benefit for patients treated with talimogene laherparepvec as compared to GM-CSF.
Source references
references
  1. citation
    Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015 Sep 1;33(25):2780-8. doi: 10.1200/JCO.2014.58.3377. Epub 2015 May 26.
    pmid
    26014293
    type
    RESULT
  2. citation
    Andtbacka RHI, Collichio F, Harrington KJ, Middleton MR, Downey G, Ӧhrling K, Kaufman HL. Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III-IV melanoma. J Immunother Cancer. 2019 Jun 6;7(1):145. doi: 10.1186/s40425-019-0623-z.
    pmid
    31171039
    type
    DERIVED
  3. citation
    Kaufman HL, Andtbacka RHI, Collichio FA, Wolf M, Zhao Z, Shilkrut M, Puzanov I, Ross M. Durable response rate as an endpoint in cancer immunotherapy: insights from oncolytic virus clinical trials. J Immunother Cancer. 2017 Sep 19;5(1):72. doi: 10.1186/s40425-017-0276-8.
    pmid
    28923101
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        -1">Evidence (T-VEC):</p> <div class="pdq-content-list"><ol id="_1425"><li>In a multinational open-label trial (<a href="/clinicaltrials/NCT00769704">NCT00769704</a>), 436 patients were randomly assigned (2:1) to receive either intralesional T-VEC or subcutaneous GM-CSF for at least 6 months or until there were no more
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      source title
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      source update dates
      1. context
        Updated: May 2, 2025
        datetime
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        display
        May 2, 2025

    Preserved source evidence · Not medical advice