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Talimogene laherparepvec

Phase 3

Melanoma | Small molecule | Oncology |Amgen Inc.|Last Updated: Jan 29, 2026

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Market & Valuation

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Trial Design

RandomizedACTIVE_CONTROLLEDDMCBiomarker
Total Trials4
Total Enrollment787

FDA Designations

No designations recorded

Clinical trial landscape

Talimogene laherparepvec · 16 trials · 29 indications

Phase 3 1Phase 2 5Phase 1 9Early Phase 1 1
NCT00769704Efficacy and Safety Study of Talimogene Laherparepvec Compared to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in MelanomaMelanoma
COMPLETED437 Analytics
PHASE3COMPLETED
Efficacy and Safety Study of Talimogene Laherparepvec Compared to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in Melanoma
MelanomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Durable Response Rate
From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.

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.

pCR rate defined as the proportion of subjects with pathologic necrosis ≥ 90%
Weeks 12-14
Objective Response Rate (ORR) Per Modified RECIST v1.1
Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months

ORR was defined as the incidence of a best overall response (BOR) of complete response (CR) or partial response (PR) per modified RECIST v1.1: * CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. All lymph nodes must have been non-pathological in size (\< 10mm short axis). * PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. * Non-CR/Non-progressive disease (PD): Persistence of 1 or more non-target lesion(s).

Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Objective Response Rate
Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at primary completion = 59 weeks (min 3 to max 116 weeks)

A univariate logistic regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of objective response. Response was assessed according to the modified version of the World Health Organization (WHO) response criteria. Objective response rate (ORR) was defined as the percentage of participants with a complete response (CR) or partial response (PR) according to the modified WHO criteria. The unadjusted odds ratio of log2(baseline intratumoral CD8+ cell density) for objective response rate is reported.

Recurrence-Free Survival (RFS)
24 months after last participant was randomized (data cutoff date of 30 April 2019)

Recurrence free survival (RFS) is defined as the time from randomization to the date of event, and is presented as a Kaplan Meier estimate of time to events. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without a histopathology tumor-free margin (R0) surgical outcome or those who withdrew prior to surgery were considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment.

Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) During the First Three Cycles
Cycles 1 and 2 on days 1 (pre-dose and 1, 4, and 8 hours post-dose), 2, 3, 8, and 15 (cycle 1 only), cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).

Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in blood or urine at any time during cycles 1 to 3 is reported. The first cycle was 21 days in length, and subsequent cycles were 14 days in length.

Number of patients with treatment-related toxicities by maximum observed grade
Up to 2.5 years

Treatment-related toxicities will be assessed according to NCI CTCAE v4.03, for all patients who receive at least one dose of study treatment. The distribution for the maximum observed grade for each adverse event will be tabulated and reported with 95% confidence interval

Maximum tolerated volume
Up to 2.5 years

The maximum tolerated volume will be the highest volume (up to 4mL) that results in \<=1 dose limiting toxicity (DLT) in 6 treated patients for the chemotherapy group. At least 15 patients will be treated in the chemotherapy cohort and at least 6 patients will be treated in the endocrine therapy cohort.

Phase 1b: Number of Subjects With Dose Limiting Toxicities (DLTs)
14 weeks

A DLT is defined as any of the following talimogene laherparepvec-related toxicity or related to the combination of talimogene laherparepvec and radiation therapy during treatment and up to 4 weeks after the last talimogene laherparepvec injection: Grade 3 or greater immune-mediated adverse events, Grade 3 or greater allergic reactions, any grade plasmacytoma, any other unexpected grade 3 or greater hematologic or non-hematologic toxicity, with the exceptions of: any grade of alopecia, expected radiation related skin toxicity of any grade, Grade 3 arthralgia or myalgia, brief (\< 1 week) grade 3 fatigue, Grade 3 fever, Grade 3 diarrhea or vomiting responding to supportive case.

Phase 2: Pathologic Tumor Necrosis Rate
14 weeks

Pathologic tumor necrosis rate is defined as the percentage of subjects with pathologic tumor necrosis ≥ 95%.

Number of Participants With Dose Limiting Toxicities (DLTs)
14 weeks

A DLT is defined as any of the following talimogene laherparepvec-related toxicity or related to the combination of talimogene laherparepvec and radiation therapy during treatment and up to 4 weeks after the last talimogene laherparepvec injection: Grade 3 or greater immune-mediated adverse events, Grade 3 or greater allergic reactions, any grade plasmacytoma, any other unexpected grade 3 or greater hematologic or non-hematologic toxicity, with the exceptions of: any grade of alopecia, expected radiation related skin toxicity of any grade, Grade 3 arthralgia or myalgia, brief (\< 1 week) grade 3 fatigue, Grade 3 fever, Grade 3 diarrhea or vomiting responding to supportive case.

Pathologic Tumor Necrosis Rate
14 weeks

Pathologic tumor necrosis rate is defined as the percentage of subjects with pathologic tumor necrosis ≥ 90%.

Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
From Day 1 up to the start of Cycle 3 (each cycle is 21 days)

Toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be related to either treatment: * Grade ≥ 4 neutropenia (absolute neutrophil count \[ANC\] \< 500/μl) lasting ≥ 7 days * Grade ≥ 3 febrile neutropenia * Grade ≥ 4 thrombocytopenia * Grade ≥ 4 anemia * Grade ≥ 4 rash * Serious herpetic events * Grade ≥ 3 symptomatic hepatic toxicities that do not resolve to Grade ≤ 2 within 48 hours or Grade ≥ 3 asymptomatic hepatic toxicities that do not resolve to Grade ≤ 1 within 3 weeks of onset * Grade ≥ 3 non-hematologic, non-hepatic organ toxicity * Grade 5 toxicity (ie, death) * Any other intolerable toxicity leading to permanent discontinuation of treatment DLTs were to occur within the DLT evaluation period, defined as the period between the initial 10\^6 PFU/mL dose and 3 weeks following the initial 10\^8 PFU/mL dose or the start of Cycle 3, whichever occurred first.

Percentage of Participants Who Experienced a Dose-limiting Toxicity (DLT)
Day 1 to Day 35

All toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0: * Grade 1: Mild * Grade 2: Moderate * Grade 3: Severe/medically significant but not immediately life-threatening * Grade 4: Life-threatening * Grade 5: Death related to adverse event The occurrence of any of the below was considered a DLT, if judged to be related to talimogene laherparepvec: * Grade 4 non-hematologic toxicity * Grade 3 non-hematologic toxicity that lasted \> 3 days despite optimal supportive care * Any ≥ grade 3 non-hematologic laboratory value if medical intervention was required, the abnormality led to hospitalization or the abnormality persisted for \> 1 week unless deemed not clinically important per both investigator \& sponsor * Febrile neutropenia grade 3/4 * Thrombocytopenia \< 25 x 10\^9/L associated with bleeding event that required intervention * Serious herpetic event * Grade 5 toxicity * Any intolerable toxicity that led to permanent discontinuation of talimogene laherparepvec

Number of Participants Who Experienced One or More Dose Limiting Toxicities (DLTs)
Day 1 to Day 35

DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4 Events were considered DLTs, if judged by the investigator to be related to study treatment: Grade 4 non-hematologic toxicity Grade 3 non-hematologic toxicity lasting \> 3 days despite optimal supportive care (grade 3 fatigue not a DLT) Grade 3 or higher non-hematologic laboratory value reported as an adverse event if: medical intervention is required, or abnormality leads to hospitalization, or abnormality persists for \> 1 week (Laboratory values that persist for \> 1 week but are deemed not clinically important per both investigator and sponsor were not considered DLTs) Febrile neutropenia grade 3 or 4 Thrombocytopenia \< 25 x 10\^9/L associated with bleeding event requiring intervention Serious herpetic event (eg, herpetic encephalitis, encephalomyelitis, or disseminated herpetic infection) Grade 5 toxicity Any other intolerable toxicity leading to permanent discontinuation of study treatment

Durable Response Rate (DRR) Using Modified World Health Organization (WHO) Response Criteria
Day 1 up to the maximum time on treatment or follow-up at primary data cutoff date (03 August 2020): 89.1 weeks of treatment and 37 months of follow-up

DRR using WHO response criteria was defined as the percentage of participants who experienced objective response (complete response \[CR\] or partial response \[PR\]) lasting continuously for ≥ 6 months that starting any time within 12 months of initiating treatment. CR: Complete disappearance of all index lesions, including any new tumors which might have appeared. PR: Achieving a 50% or greater reduction in the SPD of the perpendicular diameters of all index lesions at the time of assessment as compared to the sum of the products of the perpendicular diameters of all index lesions at baseline (Day 1).

Number of Participants With a Dose Limiting Toxicity (DLT)
First 6 weeks after the initial administration of talimogene laherparepvec and pembrolizumab in combination

The following toxicities (graded per the Common Terminology Criteria for Adverse Events v 4.0) were considered DLTs if judged by the investigator to be related to either study drug: * grade 4 non-hematologic (non-laboratory) toxicity * ≥ grade 3 pneumonitis * grade 3 non-hematologic toxicity for \> 3 days with optimal supportive care * grade 3 fatigue was not classified as DLT, regardless of duration * any ≥ grade 3 non-hematologic laboratory value if: * medical intervention was required, * the abnormality led to hospitalization, or * the abnormality persisted at ≥ grade 3 for \> 1 week unless deemed not clinically important by investigator and sponsor * grade 3 or 4 febrile neutropenia * thrombocytopenia \< 25 x 10⁹/L associated with bleeding event requiring intervention * serious herpetic event: herpetic encephalitis, encephalomyelitis, or disseminated herpetic infection * grade 5 toxicity * other intolerable toxicity leading to permanent discontinuation of either study drug.

Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)
Cycle 1 and Cycle 2: Day 1 to Day 21

All toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: * Grade 1: Mild * Grade 2: Moderate * Grade 3: Severe or medically significant but not immediately life threatening * Grade 4: Life threatening consequences * Grade 5: Death related to adverse event (AE) The occurrence of specific pre-defined toxicities during the DLT evaluation period were considered a DLT if judged by the investigator to be related to talimogene laherparepvec and/or pembrolizumab. All Grade 5 toxicities, intolerable toxicities that lead to permanent discontinuation of talimogene laherparepvec and/or pembrolizumab and Grade 3 or higher AEs related to talimogene laherparepvec and/or pembrolizumab that resulted in a study treatment delay by \> 2 weeks were considered DLTs.

Part 2 Only: Objective Response Rate (ORR) Per Modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST).
Up to 154 weeks

ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) per modified irRC-RECIST. * CR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation.

Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Day 1 to 30 days post-last dose of talimogene laherparepvec or pembrolizumab, whichever is later. The maximum duration of talimogene laherparepvec treatment was 102.4 weeks and pembrolizumab treatment was 109.3 weeks in Part 2.

A TEAE was defined as an event that emerged during treatment, having been absent pretreatment, or worsened relative to the pretreatment state. A treatment-related TEAE was defined as a TEAE that was suspected to be related to the study treatment.

Phase 1b: Number of Participants With Dose-limiting Toxicities
The DLT evaluation period was 6 weeks from the initial administration of ipilimumab (week 6 to 12).

A DLT was defined as any toxicity related to study drug which met any of the following criteria based on Common Terminology Criteria for Adverse Events version 3.0: * treatment-related non-laboratory adverse events (AE) ≥ grade 4 * ≥ grade 4 immune-mediated dermatitis * ≥ grade 4 immune-mediated endocrinopathy (except autoimmune thyroiditis) * ≥ grade 3 immune-mediated enterocolitis * ≥ grade 3 immune-mediated hepatitis (except grade 3 that resolved to grade 1 or baseline within 28 days of onset) * ≥ grade 3 immune-mediated neuropathy * ≥ grade 3 other immune-mediated AEs including hemolytic anemia, angiopathy, myocarditis, pericarditis, temporal arteritis, or vasculitis, autoimmune thyroiditis (except grade 3 that resolved to grade 1 or baseline within 28 days of onset), blepharitis, conjunctivitis, episcleritis, iritis, scleritis, or uveitis, pancreatitis, meningitis, arthritis or polymyalgia rheumatic, nephritis, pneumonitis, psoriasis or leukocytoclastic vasculitis.

Phase 2: Objective Response Rate
Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively.

Objective response rate is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) according to the modified immune-related response criteria (irRC) assessed by the investigator. Tumors were examined clinically and by computed tomography (CT) or magnetic resonance imaging (MRI). CR: Complete disappearance of all lesions and no new lesions; Any pathological lymph nodes reduced in short axis to \<10 mm. PR: Decrease in tumor burden ≥ 50% relative to baseline. Response must have been confirmed by a repeat, consecutive assessment ≥ 4 weeks from the date first documented. Participants who did not have any follow-up tumor assessments were regarded as non-responders.

Rate of residual cancer burden class 0 and 1 (RCB0/1)
24 months since first patient in

As a dichotomous measure of tumor response, RCB 0/1 yes vs. no., after neoadjuvant treatment, according to the MD Anderson Cancer Center procedures, as per local assessment.

Secondary Endpoints

Overall Survival
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.
Objective Response Rate
From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
Duration of Response
From randomization until the data cut-off date of 21 December 2012; median follow-up time was 20 months.
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
GM-CSFACTIVE_COMPARATORGranulocyte 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.
Talimogene LaherparepvecEXPERIMENTALParticipants 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.
Expansion PilotEXPERIMENTALPatients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec. Weekly injections of talimogene laherparepvec will be continued until surgery. Surgery will be performed 4-6 weeks from the end of radiation therapy to allow for resolution of acute toxicities per current standard of care
Cohort 1 - Locally Recurrent/Metastatic - Primary ResistanceEXPERIMENTALIncludes participants who received anti-PD1 therapy in the locally recurrent/metastatic setting and experienced a best overall response of disease progression or stable disease prior to confirmed disease progression. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.
Cohort 2 - Locally Recurrent/Metastatic - Acquired ResistanceEXPERIMENTALIncludes participants who received anti-PD-1 therapy in the locally recurrent/metastatic setting and experienced confirmed disease progression following a complete or partial response on anti-PD-1 therapy. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.
Cohort 3 - Adjuvant Setting -Disease Free Interval < 6 monthsEXPERIMENTALIncludes participants who received anti-PD-1 therapy in the adjuvant setting and experienced confirmed disease progression following a disease-free interval of \< 6 months after starting the adjuvant anti-PD-1 therapy. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.
Cohort 4 - Adjuvant Setting -Disease Free Interval ≥ 6 monthsEXPERIMENTALIncludes participants who received anti PD-1 therapy in the adjuvant setting and experienced confirmed disease progression following a disease-free interval of ≥ 6 months after starting the adjuvant PD-1 inhibitor. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.
SurgeryOTHERSurgical resection of melanoma tumor lesion(s)
Cohort I (talimogene laherparepvec, chemotherapy)EXPERIMENTALPatients receive talimogene laherparepvec intra-tumorally (IT) every 2 weeks for the first 10 weeks and every 3 weeks thereafter along with one of the following chemotherapies: paclitaxel (IV), nab-paclitaxel IV, or gemcitabine / carboplatin IV. Cycles repeat every 21 days until disease progression or unacceptable toxicity
Cohort II (talimogene laherparepvec, endocrine therapy)EXPERIMENTALPatients receive talimogene laherparepvec intra-tumorally (IT) every 2 weeks for the first 10 weeks and every 3 weeks thereafter along with letrozole PO, anastrazole PO, exemestane PO, tamoxifen PO on days 1-21 or fulvestrant IM every 2 weeks for 3 doses then every 4 weeks for the subsequent courses. Cycles repeat every 28 days until disease progression or unacceptable toxicity
TreatmentEXPERIMENTALTalimogene Laherparepvec in combination with radiotherapy Talimogene Laherparepvec Dose Levels: • Initial dose for all = talimogene laherparepvec up to 4.0 mL of 106 PFU/mL
Talimogene Laherparepvec in combination with radiotherapy-Phase I CohortEXPERIMENTALTalimogene Laherparepvec Dose Levels: Dose 0 = talimogene laherparepvec up to 8.0 mL of 108 PFU/mL dosed weekly Dose -1 = talimogene laherparepvec up to 8.0 mL of 108 PFU/mL dosed every 2 weeks
Talimogene Laherparepvec in combination with radiotherapy-Phase II CohortACTIVE_COMPARATORDose 0 = talimogene laherparepvec up to 8.0 mL of 108 PFU/mL dosed weekly
Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)EXPERIMENTALParticipants with TNBC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10\^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10\^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.
Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC)EXPERIMENTALParticipants with CRC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10\^6 PFU/mL on Day 1 of Cycle 1 and 10\^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.
Talimogene Laherparepvec (TVEC)EXPERIMENTALThe first dose of talimogene laherparepvec will be administered at a dose of up to 4.0 mL of 10ᶺ6 PFU/mL followed by a dose of up to 4.0 mL of 10ᶺ8 PFU/mL 21 days (+3 days) later. Subsequent doses of up to 4.0 mL of 10ᶺ8 PFU/mL will be administered every 14 days (± 3 days) thereafter. Cohorts will be assigned as follows: Cohort A1 (age 12 to ≤ 21 years). Cohort B1 (age 2 to \< 12 years). The DLRT will review the safety data of the first 3 subjects in the older age cohort A1 to decide if the younger age cohort B1 can be opened for enrollment. If dose de-escalation is needed and if permissible based on the incidence of DLTs, additional DLT-evaluable subjects will be enrolled and treated at a lower dose level of talimogene laherparepvec. Dose de-escalation cohorts will be assigned as follows and the same DLT rules will be applied: Cohort A2 (age 12 to ≤ 21 years), Cohort B2 (age 2 to \< 12 years).
Talimogene Laherparepvec + PembrolizumabEXPERIMENTALTalimogene laherparepvec is administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 3 weeks after the initial dose and every 3 weeks (Q3W) thereafter. Pembrolizumab is administered by intravenous infusion at a dose of 200 mg Q3W after the initial dose. Participants are treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Phase Ib/II Talimogene LaherparepvecEXPERIMENTALTalimogene Laherparepvec
Phase Ib/II Talimogene Laherparepvec + PembrolizumabEXPERIMENTALCombination treatment of Talimogene Laherparepvec and Pembrolizumab
Phase 1b: Talimogene Laherparepvec + IpilimumabEXPERIMENTALParticipants received talimogene laherparepvec at an initial dose of 10⁶ plaque-forming units (PFU)/mL injected into 1 or more skin, nodal, or subcutaneous tumors. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until complete response (CR), all injectable tumors had disappeared, confirmed disease progression per the modified immune-related response criteria (irRC), or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab administered intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6).
Phase 2: IpilimumabACTIVE_COMPARATORParticipants received ipilimumab 3 mg/kg intravenously every 3 weeks for a total of 4 infusions starting at week 1.
Phase 2: Talimogene Laherparepvec + IpilimumabEXPERIMENTALParticipants received talimogene laherparepvec at an initial dose of 10⁶ PFU/mL injected into 1 or more skin, nodal, or subcutaneous tumors. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until CR, all injectable tumors had disappeared, confirmed disease progression per the modified irRC, or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6).
Talimogene laherparepvec + AtezolizumabEXPERIMENTAL1. Talimogene laherparepvec: Cycle 1 - 10\^6 PFU/mL. Cycle 2, 3, 4 \& 5 - 10\^8 PFU/mL. 2. Atezolizumab 840 mg

Interventions

NameTypeDescription
Talimogene laherparepvecBIOLOGICALUp to 4 mL of 10⁸ pfu/mL/per intratumoral injection
GM-CSFBIOLOGICAL125 µg/m² subcutaneous injection
Neoadjuvant RadiationRADIATIONTreatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given. Patients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec
SurgeryPROCEDURESurgery will be performed 4-6 weeks from the end of radiation therapy to allow for resolution of acute toxicities per current standard of care
PembrolizumabDRUGIntravenous (IV) infusion.
Immediate surgical resection of melanoma lesion(s)PROCEDURESurgical resection of melanoma tumor lesion(s) will be performed after randomization any time during weeks 1 to 6.
AnastrozoleDRUGGiven PO
ExemestaneDRUGGiven PO
FulvestrantDRUGGiven IM
LetrozoleDRUGGiven PO
PaclitaxelDRUGGiven IV
TamoxifenDRUGGiven PO
Nab paclitaxelDRUGGiven IV
GemcitabineDRUGGiven IV
CarboplatinDRUGGiven IV
RadiotherapyRADIATIONConcurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines.
AtezolizumabBIOLOGICALA monoclonal antibody given by intravenous injection.
IpilimumabDRUGIpilimumab administered intravenously every 3 weeks for a total of 4 infusions.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites83

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...

Countries:United StatesCanadaSouth AfricaUnited KingdomAustraliaFranceGermanyGreeceItalyNetherlandsPolandSpainAustriaBelgiumHungaryRussiaBrazilSwitzerlandJapanSouth Korea
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Frequently asked questions about Talimogene laherparepvec

What is Talimogene Laherparepvec used for?

Talimogene Laherparepvec is an investigational oncology therapy being studied for completely resectable Stage IIIB, IIIC, or IVM1a melanoma, unresected Stage IIIb to IVM1c melanoma, carcinoma of the head and neck, hepatocellular carcinoma, soft tissue sarcoma, and advanced non-CNS tumors. It is currently in Phase 1 clinical development.

What does Talimogene Laherparepvec target?

Talimogene Laherparepvec is a gene therapy, classified under the -vec/-gene target class. It is being studied for its effects in multiple solid tumor types, including melanoma, head and neck carcinoma, hepatocellular carcinoma, and soft tissue sarcoma, though its specific molecular target is not detailed.

Who makes Talimogene Laherparepvec?

Talimogene Laherparepvec is being developed by Amgen Inc., a biopharmaceutical company traded on NASDAQ under the ticker AMGN. The drug is currently in Phase 1 clinical trials for several oncology indications.

What phase is Talimogene Laherparepvec in?

Talimogene Laherparepvec is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. Four Phase 1 trials have been completed, with a total enrollment of 787 patients across studies in melanoma, head and neck cancer, liver cancer, and other advanced tumors.

What clinical trials is Talimogene Laherparepvec in?

Talimogene Laherparepvec has been studied in four completed Phase 1 trials: NCT02509507 in hepatocellular carcinoma and liver metastases, NCT02626000 in head and neck carcinoma, NCT02756845 in advanced non-CNS tumors in children, and NCT03256344 in triple negative breast cancer and colorectal cancer with liver metastases.

Is Talimogene Laherparepvec the same as Imlygic?

Talimogene Laherparepvec is also known by the brand name Imlygic, which is approved for melanoma. However, the clinical trials listed here are investigational Phase 1 studies in additional indications, and the drug remains in clinical development for those uses.