Advances in Intralesional Therapy for Locoregionally Advanced and Metastatic Melanoma: Five Years of Progress
Abstract
:Simple Summary
Abstract
1. Introduction
2. Xanthene Dyes
2.1. PV-10
2.2. Cytokines
2.2.1. Interleukin-2 (IL-2, Aldesleukin)
2.2.2. Tavokinogene Telseplasmid (Tavo)
2.3. Antibody–Cytokine Fusion Proteins
2.3.1. Darleukin (L19IL2)
2.3.2. Daromun (L19IL2 and L19TNF)
2.4. Oncolytic Viral Therapies
2.4.1. Talimogene Laherparepvec
2.4.2. RP1 (Vusolimogene Oderparepvec)
2.4.3. OrienX010
2.4.4. ONCOS-102 (Ad5/3-Δ24-GM-CSF)
2.4.5. BT-001
2.4.6. Canerpaturev (C-REV, TBI-1401, HF10)
2.4.7. Coxsackievirus A21 (CVA21, CAVATAK, V937, Gebasaxturev)
2.4.8. PVSRIPO (Lerapolturev)
2.4.9. OBP-301 (Telomelysin)
2.4.10. Voyager-V1 (VV1, VSV-IFNβ-NIS)
2.4.11. Ad-p53
2.4.12. RheoSwitch Therapeutic System
2.5. Toll-like Receptor 9 (TLR9) Agonists
2.5.1. Tilsotolimod (IMO-2125)
2.5.2. SD-101
2.5.3. Vidutolimod (CMP-001)
2.5.4. Cavrotolimod (AST-008)
2.6. Toll-like Receptor 7/8 (TLR 7/8) Agonists
NKTR-262
2.7. Immune Checkpoint Inhibitors
2.8. Other Therapeutics
2.8.1. LL37
2.8.2. Hiltonol (Polyinosinic-Polycytidylic Acid-Poly-I-Lysine Carboxymethylcellulose, Poly-ICLC)
2.8.3. APX005M
2.8.4. Dendritic Cell Therapy
2.8.5. INT230-6
2.8.6. Polidocanol
3. Conclusions
Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Clinical Trial Number | Phase | Regimen | Melanoma Population | Intralesional Dosing Schedule | Preliminary Results |
---|---|---|---|---|---|
NCT02557321 | 1b/2 | IT PV-10 + IV pembro vs. IV pembro alone | ICI-Naïve and ICI-refractory, unresectable, stage III–IV | Q3W x 5C | |
NCT03474497 | 1/2 | IT IL-2 + IV ICI + hypofractionated XRT | PD-1/L1-refractory, stage IV | 2x/W x 4C | - |
NCT03928275 | 2/3 | IT IL-2 vs. IT IL-2 + IT BCG | Stage IIIC-IVM1a | Q2W x 4C | - |
NCT03132675 | 2 | IT Tavo-EP + IV pembro | Anti-PD-1-refractory, unresectable, stage III–IV | Days 1, 5, 8, Q6W, up to 18C |
|
NCT02076646 | 1/2 | IT L19IL2 + IV DTIC vs. IV DTIC alone | Stage IV (M1a-b in phase 2) | Days 1, 8, 15 Q3W | - |
NCT03567889 | 3 | IT Daromun + surgery + IV ID adjuvant vs. surgery + IV ID adjuvant | Neoadjuvant, resectable stage IIIB-C | Q1W, up to 4C | - |
NCT02938299 | 3 | IT Daromun + surgery vs. surgery | Neoadjuvant, resectable stage IIIB-C | Q1W, up to 4C | - |
NCT04427306 | 2 | IT T-VEC + surgery | Neoadjuvant, resectable, high-risk | Not specified | - |
NCT04068181 | 2 | IT T-VEC + IV pembro | Anti-PD-1-refractory, unresectable, stage IIIB-IV | Q3W, up to 35C |
|
NCT04330430 | 2 | IT T-VEC + IV nivo | Neoadjuvant, resectable stage IIIB-IVM1a | Q3W x 1C then Q2W x 3C | - |
NCT03842943 | 2 | IN T-VEC + IV pembro | Neoadjuvant, clinically node-positive, resectable, stage III | Q3W up to 6 mos. | - |
NCT02819843 | 2 | IT T-VEC ± XRT | Unresectable, stage IIIB-IV | Q3W x 1C then Q2W x 7C | - |
NCT03555032 | 1/2 | IT T-VEC + ILP | Amenable to ILP, stage IIIB-IVM1b | Q2-3 Weeks x 3 doses | - |
NCT03767348 | 1/2 | IT RP1 ± IV nivo | Stage IIIB-IVM1c | Not specified | |
NCT04349436 | 1b/2 | IT RP1 | Treatment-refractory, locally advanced or metastatic, solid organ transplant recipients | Q2W | - |
NCT04200040 | 2 | IT OrienX010 vs. IV DTIC | Treatment-naïve, unresectable, stage IIIB-IVM1b | Q2W | - |
NCT05561491 | 2 | IT Oncos-102 ± IV balstilimab | Anti-PD-1-refractory, unresectable or metastatic | Not specified | - |
NCT04725331 | 1/2a | IT BT-001 ± IV pembro | Locally advanced or metastatic | Not specified | - |
NCT04152863 | 2 | IT & IV CVA21 + IV pembro vs. IV pembro | ICI-naïve, stage III-IV | Day 1, 3, 5, 8 Q4W x 1C, then Q3W x up to 7C | - |
NCT04303169 | 1/2 | IT CVA21 + IV pembro + surgery vs. other investigational drugs + IV pembro + surgery | Neoadjuvant, treatment-naïve, resectable, stage IIIB-D | Not specified | - |
NCT04577807 | 2 | IT PVSRIPO ± IV anti-PD-1 therapy | Anti-PD-1/L1-refractory, unresectable, stage III-IVM1b | Q1W x 7C then Q3-4W | - |
NCT03190824 | 2a | IT OBP-301 | Unresectable, stage IIIB-IV | Q2W up to 13C | - |
NCT04291105 | 2 | IT and IV VV1 + IV cemiplimab ± ipi | Anti-PD-1/L1-refractory, advanced or metastatic | Q4W x 1C, then Q3W | - |
NCT03544723 | 2 | IT Ad-p53 + IV ID ICI | Recurrent or metastatic | Not specified | - |
NCT01397708 | 1/2 | IT RheoSwitch | Unresectable, stage III-IV | Q3W up to 6 C |
|
NCT04698187 | 2 | IT vidutolimod + IV nivo | Anti-PD-1-refractory, unresectable or metastatic | Q1W x 7C then Q3W | - |
NCT04695977 | 2/3 | IT vidutolimod + IV nivo vs. IV nivo | Treatment-naïve, unresectable or metastatic | Q1W x 7C then Q3W | - |
NCT04401995 | 2 | IT vidutolimod + IV nivo vs. IV nivo | Neoadjuvant, palpable nodal disease or nodal recurrence, stage IIIB-D | Q1W x 7C | - |
NCT04708418 | 2 | IT vidutolimod + IV pembro + surgery vs. IV pembro + surgery | Neoadjuvant, resectable, stage III N1b-N3c | Day 1, 8, 15 Q3W x 2C then Q3W x 4C | - |
NCT03684785 | 1b/2 | IT cavrotolimod + IV pembro | Anti-PD-1/L1-refractory, locally advanced or metastatic | Not specified |
|
NCT02857569 | 1/2 | IT ipi + IV nivo vs. IV ipi + IV nivo | Unresectable, stage III-IV | Q3W up to 4C | - |
NCT03755739 | 2/3 | IT ID ICIs vs. trans-arterial ID ICIs vs. IV ID ICIs | Advanced | Q3W | - |
NCT02225366 | 1/2 | LL37 | Unresectable, stage IIIB-IVA | Q1W up to 8C | - |
NCT02423863 | 2 | IT hiltonol + IM hiltonol ± IV anti-PD-1/L1 | Unresectable, advanced | IT Day 1, 3, 5 x 1W then IM 2x/W | - |
NCT02706353 | 1/2 | IT APX005M + IV pembro | ICI-naïve, unresectable, stage III-IVM1c | Q3W up to 4C | - |
NCT03325101 | 1b/2 | IT DCs + cryosurgery + IV pembro | Anti-PD-1/L1-refractory, unresectable, stage III-IV | Apheresis then Q3W x 2C | - |
NCT03058289 | 1/2 | IT INT230-6 ± IV ICI | Treatment-refractory, metastatic | Q4W x 5C |
|
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DePalo, D.K.; Zager, J.S. Advances in Intralesional Therapy for Locoregionally Advanced and Metastatic Melanoma: Five Years of Progress. Cancers 2023, 15, 1404. https://doi.org/10.3390/cancers15051404
DePalo DK, Zager JS. Advances in Intralesional Therapy for Locoregionally Advanced and Metastatic Melanoma: Five Years of Progress. Cancers. 2023; 15(5):1404. https://doi.org/10.3390/cancers15051404
Chicago/Turabian StyleDePalo, Danielle K., and Jonathan S. Zager. 2023. "Advances in Intralesional Therapy for Locoregionally Advanced and Metastatic Melanoma: Five Years of Progress" Cancers 15, no. 5: 1404. https://doi.org/10.3390/cancers15051404