Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT00769704 | Efficacy and Safety Study of Talimogene Laherparepvec Compared to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in Melanoma | PHASE3 | COMPLETED | 437 | — | — | Apr 1, 2009 | Sep 1, 2014 | Jul 13, 2016 | 83 | United States, Canada +2 |
| NCT04068181 | Talimogene Laherparepvec With Pembrolizumab in Melanoma Following Progression on Prior Anti-PD-1 Based Therapy (MASTERKEY-115) (Mk-3475-A07/KEYNOTE-A07). | PHASE2 | COMPLETED | 72 | — | — | Jan 22, 2020 | Feb 26, 2024 | Jan 7, 2025 | 46 | United States, Australia +9 |
| NCT02014441 | Single-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec | PHASE2 | COMPLETED | 61 | — | — | Apr 7, 2014 | Apr 19, 2018 | Nov 20, 2019 | 14 | United States, Canada |
| NCT01740297 | Ipilimumab With or Without Talimogene Laherparepvec in Unresected Melanoma | PHASE1 | COMPLETED | 217 | — | — | Feb 7, 2013 | Mar 9, 2021 | May 14, 2024 | 40 | United States, France +1 |
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.
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).
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| GM-CSF | ACTIVE_COMPARATOR | 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. |
| Talimogene Laherparepvec | EXPERIMENTAL | 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. |
| Cohort 1 - Locally Recurrent/Metastatic - Primary Resistance | EXPERIMENTAL | Includes 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 Resistance | EXPERIMENTAL | Includes 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 months | EXPERIMENTAL | Includes 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 months | EXPERIMENTAL | Includes 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. |
| Phase 1b: Talimogene Laherparepvec + Ipilimumab | EXPERIMENTAL | Participants 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: Ipilimumab | ACTIVE_COMPARATOR | Participants received ipilimumab 3 mg/kg intravenously every 3 weeks for a total of 4 infusions starting at week 1. |
| Phase 2: Talimogene Laherparepvec + Ipilimumab | EXPERIMENTAL | Participants 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). |
| Name | Type | Description |
|---|---|---|
| Talimogene laherparepvec | BIOLOGICAL | Up to 4 mL of 10⁸ pfu/mL/per intratumoral injection |
| GM-CSF | BIOLOGICAL | 125 µg/m² subcutaneous injection |
| Pembrolizumab | DRUG | Intravenous (IV) infusion. |
| Ipilimumab | DRUG | Ipilimumab administered intravenously every 3 weeks for a total of 4 infusions. |
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...