Download PDF
Aktuelle Dermatologie 2022; 48(03): 92-101
DOI: 10.1055/a-1700-9298
Übersicht

Die Systemtherapie des malignen Melanoms

Systemic Treatment for Malignant Melanoma
Nathalie Ritter
Klinikum Nürnberg, Hautklinik, Universitätsklinik für Dermatologie der Paracelsus Medizinischen Privatuniversität, Nürnberg
,
Lucia Peeken
Klinikum Nürnberg, Hautklinik, Universitätsklinik für Dermatologie der Paracelsus Medizinischen Privatuniversität, Nürnberg
,
Erwin S. Schultz
Klinikum Nürnberg, Hautklinik, Universitätsklinik für Dermatologie der Paracelsus Medizinischen Privatuniversität, Nürnberg
,
Dirk Debus
Klinikum Nürnberg, Hautklinik, Universitätsklinik für Dermatologie der Paracelsus Medizinischen Privatuniversität, Nürnberg
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Zusammenfassung

In den vergangenen 10 Jahren wurde die Systemtherapie des malignen Melanoms durch die Zulassung neuer Substanzen revolutioniert. In der vorliegenden Übersicht werden zunächst die aktuellen adjuvanten Therapiemöglichkeiten beschrieben, anschließend werden der Kenntnisstand zur neoadjuvanten Therapie dargestellt und schließlich die Behandlungsoptionen im inoperablen Stadium beleuchtet.

Abstract

In the past 10 years, systemic treatment for malignant melanoma has been revolutionized with the approval of new substances. In the present overview, the current adjuvant therapy options are first described, then the state of knowledge about neoadjuvant therapy is presented and finally the treatment options in the inoperable stage are highlighted.



Publication History

Article published online:
16 March 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Yang DD, Salciccioli JD, Marshall DC. et al. Trends in malignant melanoma mortality in 31 countries from 1985 to 2015. Br J Dermatol 2020; 183: 1056-1064
    CrossrefPubMedSearch in Google Scholar
  • 2 Krebs in Deutschland für 2015/2016, 12. Ausgabe, korrigierte Fassung vom 17.08.2020, Robert Koch-Institut, Berlin. 2019
    CrossrefPubMedSearch in Google Scholar
  • 3 Ives NJ, Suciu S, Eggermont AMM. et al. Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis. Eur J Cancer 2017; 82: 171-183
    CrossrefPubMedSearch in Google Scholar
  • 4 Eggermont AMM, Chiarion-Sileni V, Grob JJ. et al. Adjuvant Ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol 2015; 16: 522-530
    CrossrefPubMedSearch in Google Scholar
  • 5 Eggermont AMM, Chiarion-Sileni V, Grob JJ. et al. Prolonged survival in Stage III melanoma with Ipilimumab adjuvant therapy. N Engl J Med 2016; 375: 1845-1855
    CrossrefPubMedSearch in Google Scholar
  • 6 Weber J, Mandalá M, Del Vecchio M. et al. Adjuvant Nivolumab versus Ipilimumab in resected stage III or IV melanoma. N Engl J Med 2017; 377: 1824-1835
    CrossrefPubMedSearch in Google Scholar
  • 7 Ascierto P, Del Vecchio M, Mandalá M. et al. Adjuvant Nivolumab versus Ipilimumab in resected stage IIIB–C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. The Lancet Oncology 2020; 21: 1465-1477
    CrossrefPubMedSearch in Google Scholar
  • 8 Five-year outcomes with adjuvant Nivolumab (NIVO) versus Ipilimumab (IPI) in resected stage IIIB–C or IV melanoma (CheckMate 238) – Jeffrey Weber. https://smrcongress.org/agenda-2021 (abgerufen am 7.11.2021)
    PubMed
  • 9 Effectiveness study of Nivolumab compared to placebo in prevention of recurrent melanoma after complete resection of stage IIB/C melanoma (CheckMate76K). https://clinicaltrials.gov/ct2/show/NCT04099251
    PubMed
  • 10 Adjuvant Nivolumab treatment in stage II (IIA, IIB, IIC) high-risk melanoma (NivoMela). https://clinicaltrials.gov/ct2/show/NCT04309409
    PubMed
  • 11 Eggermont AMM, Blank CU, Mandalá M. et al. Adjuvant Pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med 2018; 378: 1789-1801
    CrossrefPubMedSearch in Google Scholar
  • 12 Eggermont AMM, Kicinski M, Blank CU. et al. Association between immune-related adverse events and recurrence-free survival among patients with stage III melanoma randomized to receive Pembrolizumab or placebo: a secondary analysis of a randomized clinical trial. JAMA Oncol 2020; 6: 519-527
    CrossrefPubMedSearch in Google Scholar
  • 13 Eggermont AMM, Blank CU, Mandalá M. et al. Adjuvant Pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): Distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol 2021; 643-654
    CrossrefPubMedSearch in Google Scholar
  • 14 Luke JJ, Rutkowski P, Queirolo P. et al. Pembrolizumab versus placebo after complete resection of high-risk stage II melanoma: efficacy and safety results from the KEYNOTE-716 double-blind phase III trial. Suppl Annals of Oncology 2021; 32 (Suppl. 05) S1283-S1346
    CrossrefPubMedSearch in Google Scholar
  • 15 Luke JJ (Vortragender), Plenary Session 11 – Late Breaking Clinical Abstracts, SMR. 2021 https://www.merck.com/news/new-research-for-keytruda-pembrolizumab-at-society-for-melanoma-research-smr-2021-congress-reinforces-mercks-commitment-to-patients-with-melanoma-across-stages-of-disease/ (New Research for KEYTRUDA (pembrolizumab) at Society for Melanoma Research (SMR) 2021 Congress Reinforces Merck’s Commitment to Patients With Melanoma Across Stages of Disease – Merck.com)
    PubMedSearch in Google Scholar
  • 16 Zimmer L, Livingstone E, Hassel JC. et al. Adjuvant Nivolumab plus Ipilimumab or Nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 2020; 395: 1558-1568
    CrossrefPubMedSearch in Google Scholar
  • 17 Maio M, Lewis K, Demidov L. et al. Adjuvant Vemurafenib in resected, BRAFV600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol 2018; 19: 510-520
    CrossrefPubMedSearch in Google Scholar
  • 18 Long GV, Hauschild A, Santinami M. et al. Adjuvant Dabrafenib plus Trametinib in stage III BRAF-mutated melanoma. N Engl J Med 2017; 377: 1813-1823
    CrossrefPubMedSearch in Google Scholar
  • 19 Hauschild A, Dummer R, Santinami M. et al. Long-term benefit of adjuvant Dabrafenib + Trametinib (D + T) in patients (pts) with resected stage III BRAF V600–mutant melanoma: five-year analysis of COMBI-AD. Journal of Clinical Oncology 2020; 38: 10001
    CrossrefPubMedSearch in Google Scholar
  • 20 Study to compare adjuvant immunotherapy of Bempegaldesleukin combined with Nivolumab versus Nivolumab after complete resection of melanoma in patients at high risk for recurrence (PIVOT-12). https://clinicaltrials.gov/ct2/show/NCT04410445
    PubMed
  • 21 Blank CU, Versluis JM, Reijers LM. et al. 3-year relapse-free survival (RFS), overall survival (OS) and long-term toxicity of (neo)adjuvant Ipilimumab (IPI) + Nivolumab (NIVO) in macroscopic stage III melanoma (OpACIN trial). Ann Oncol 2019; 30 (Suppl. 05)
    CrossrefPubMedSearch in Google Scholar
  • 22 Rozeman EA, Menzies AM, van Akkooi ACJ. et al. Identification of the optimal combination dosing schedule of neoadjuvant Ipilimumab plus Nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre phase 2, randomised, controlled trial. Lancet Oncol 2019; 20: 948-960
    CrossrefPubMedSearch in Google Scholar
  • 23 Blank CU, Reijers ILM, Pennington T. et al. First safety and efficacy results of PRADO: a phase II study of personalized response-driven surgery and adjuvant therapy after neoadjuvant Ipilimumab (IPI) and Nivolumab (NIVO) in resectable stage III melanoma. Journal of Clinical Oncology 2020; 38: 10002
    CrossrefPubMedSearch in Google Scholar
  • 24 Neoadjuvant Ipilimumab plus Nivolumab versus standard adjuvant Nivolumab in macroscopic stage III melanoma (NADINA). https://clinicaltrials.gov/ct2/show/NCT04949113
    PubMed
  • 25 Amaria RN, Prieto PA, Tetzlaff MT. et al. Neoadjuvant plus adjuvant Dabrafenib and Trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial. Lancet Oncol 2018; 19: 181-193
    CrossrefPubMedSearch in Google Scholar
  • 26 Neoadjuvant Vemurafenib + Cobimetinib + Atezolizumab in melanoma: NEO-VC (NEO-VC). https://clinicaltrials.gov/ct2/show/NCT02303951
    PubMed
  • 27 Robert C, Long GV, Brady B. et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2014; 372: 320-330
    CrossrefPubMedSearch in Google Scholar
  • 28 Ascierto PA, Long GV, Robert C. et al. Survival outcomes in patients with previously untreated BRAF wild-type advanced melanoma treated with Nivolumab Therapy: Three-Year Follow-up of a randomized phase 3 trial. JAMA Oncol 2019; 5: 187-194
    CrossrefPubMedSearch in Google Scholar
  • 29 Schachter J, Ribas A, Long GV. et al. Pembrolizumab versus Ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet 2017; 390: 1853-1862
    CrossrefPubMedSearch in Google Scholar
  • 30 Robert C, Ribas A, Schachter J. et al. Pembrolizumab versus Ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol 2019; 20: 1239-1251
    CrossrefPubMedSearch in Google Scholar
  • 31 Robert C (Vortragender), Plenary Session 11 – Late Breaking Clinical Abstracts, SMR. 2021 https://www.merck.com/news/new-research-for-keytruda-pembrolizumab-at-society-for-melanoma-research-smr-2021-congress-reinforces-mercks-commitment-to-patients-with-melanoma-across-stages-of-disease/ (New Research for KEYTRUDA (pembrolizumab) at Society for Melanoma Research (SMR) 2021 Congress Reinforces Merck’s Commitment to Patients With Melanoma Across Stages of Disease – Merck.com)
    PubMedSearch in Google Scholar
  • 32 Wolchok JD, Chiarion-Sileni V, Gonzalez R. et al. Overall survival with combined Nivolumab and Ipilimumab in advanced melanoma. N Engl J Med 2017; 377: 1345-1356
    CrossrefPubMedSearch in Google Scholar
  • 33 Larkin J, Chiarion-Sileni V, Gonzalez R. et al. Five-year survival with combined Nivolumab and Ipilimumab in advanced melanoma. N Eng J Med 2019; 381: 1535-1546
    CrossrefPubMedSearch in Google Scholar
  • 34 Wolchok JD, Chiarion-Sileni V, Gonzalez R. et al. CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma. Journal of Clinical Oncology 2021; 39: 9506
    CrossrefPubMedSearch in Google Scholar
  • 35 Margolin KA, Tawbi HA, Forsyth PA. et al. CheckMate 204: 3-year outcomes of treatment with combination Nivolumab (NIVO) plus Ipilimumab (IPI) for patients (pts) with active melanoma brain metastases (MBM). Annals of Oncology 2021; 32 (Suppl. 05) S867-S905
    CrossrefPubMedSearch in Google Scholar
  • 36 Lebbe C, Meyer N, Mortier L. et al. Two dosing regimens of Nivolumab plus Ipilimumab for advanced melanoma: 3-year results of CheckMate 511. Journal of Clinical Oncology 2021; 39: 9516-9516
    CrossrefPubMedSearch in Google Scholar
  • 37 Long GV, Flaherty KT, Stroyakovskiy D. et al. Dabrafenib plus Trametinib versus Dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. Ann Oncol 2017; 28: 1631-1639
    CrossrefPubMedSearch in Google Scholar
  • 38 Robert C, Grob JJ, Stroyakovskiy D. et al. Five-year outcomes with Dabrafenib plus Trametinib in metastatic melanoma. N Engl J Med 2019; 381: 626-636
    CrossrefPubMedSearch in Google Scholar
  • 39 Robert C, Karaszewska B, Schachter J. et al. Improved overall survival in melanoma with combined Dabrafenib and Trametinib. N Engl J Med 2015; 372: 30-39
    CrossrefPubMedSearch in Google Scholar
  • 40 Ascierto PA, McArthur GA, Dréno B. et al. Cobimetinib combined with Vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol 2016; 17: 1248-1260
    CrossrefPubMedSearch in Google Scholar
  • 41 Dréno B, Ascierto PA, McArthur GA. et al. Efficacy and safety of Cobimetinib (C) combined with Vemurafenib (V) in patients (pts) with BRAFV600 mutation-positive metastatic melanoma: analysis from the 4-year extended follow-up of the phase 3 coBRIM study. Journal of Clinical Oncology 2018; 36: 9522
    CrossrefPubMedSearch in Google Scholar
  • 42 Ascierto PA, Dréno B, Larkin J. et al. 5-year outcomes with Cobimetinib plus Vemurafenib in BRAFV600 mutation-positive advanced melanoma: Extended follow-up of the coBRIM study. Clin Cancer Res 2021; 27: 5225-5235
    CrossrefPubMedSearch in Google Scholar
  • 43 Dummer R, Ascierto PA, Gogas HJ. et al. Overall survival in patients with BRAF-mutant melanoma receiving Encorafenib plus Binimetinib versus Vemurafenib or Encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2018; 19: 1315-1327
    CrossrefPubMedSearch in Google Scholar
  • 44 Ascierto PA, Dummer R, Gogas HJ. et al. Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of Encorafenib plus Binimetinib vs Vemurafenib or Encorafenib in patients with BRAF V600-mutant melanoma. Eur J Cancer 2020; 126: 33-44
    CrossrefPubMedSearch in Google Scholar
  • 45 Dummer R, Flaherty KT, Robert C. et al. Five-year overall survival (OS) in COLUMBUS: a randomized phase 3 trial of Encorafenib plus Binimetinib versus Vemurafenib or Encorafenib in patients (pts) with BRAF V600-mutant melanoma. Journal of Clinical Oncology 2021; 39: 9507
    CrossrefPubMedSearch in Google Scholar
  • 46 Algazi AP, Othus M, Daud AI. et al. Continuous versus intermittent BRAF and MEK inhibition in patients with BRAF-mutated melanoma: a randomized phase 2 trial. Nat Med 2020; 26: 1564-1568
    CrossrefPubMedSearch in Google Scholar
  • 47 Ugurel S, Röhmel J, Ascierto PA. et al. Survival of patients with advanced metastatic melanoma: the impact of MAP kinase pathway inhibition and immune checkpoint inhibition – update 2019. European journal of cancer 2020; 130: 126-138
    CrossrefPubMedSearch in Google Scholar
  • 48 Tarhini AA, Toor K, Chan K. et al. A matching-adjusted indirect comparison of combination Nivolumab plus Ipilimumab with BRAF plus MEK inhibitors for the treatment of BRAF-mutant advanced melanoma. ESMO Open 2021; 6: 100050
    CrossrefPubMedSearch in Google Scholar
  • 49 Keilholz U, Ascierto PA, Dummer R. et al. ESMO consensus conference recommendations on the management of metastatic melanoma: under the auspices of the ESMO Guidelines Committee. Ann Oncol 2020; 31: 1435-1448
    CrossrefPubMedSearch in Google Scholar
  • 50 Atkins MB, Lee SJ, Chmielowski B. et al. DREAMseq (doublet, randomized evaluation in advanced melanoma sequencing): A phase III trial –ECOG-ACRIN EA6134. J Clin Oncol 2021; 39
    CrossrefPubMedSearch in Google Scholar
  • 51 Ascierto PA, Mandalá M, Ferrucci PF. et al. LBA45 – first report of efficacy and safety from the phase II study SECOMBIT (SEquential COMBo Immuno and targeted therapy study). Ann Oncol 2020; 31 (Suppl. 04) S1142-S1215
    CrossrefPubMedSearch in Google Scholar
  • 52 Ascierto PA, Mandalá M, Ferrucci PF. et al. SECOMBIT: the best sequential approach with combo immunotherapy [Ipilimumab (I)/Nivolumab (N)] and combo target therapy [Encorafenib (E)/Binimetinib (B)] in patients with BRAF mutated metastatic melanoma: A phase II randomized study. Ann Oncol 2021; 32 (Suppl. 05) S1283-S1346
    CrossrefPubMedSearch in Google Scholar
  • 53 Immunotherapy with Ipilimumab and Nivolumab preceded or not by a targeted therapy with Encorafenib and Binimetinib (EBIN). https://clinicaltrials.gov/ct2/show/NCT03235245
    PubMed
  • 54 Gutzmer R, Stroyakovskiy D, Gogas H. et al. Atezolizumab, Vemurafenib, and Cobimetinib as first-line treatment for unresectable advanced BRAF V600 mutation-positive melanoma (IMspire150): primary analysis of the randomised,double-blind, placebo-controlled, phase 3 trial. Lancet 2020; 395: 1835-1844
    CrossrefPubMedSearch in Google Scholar
  • 55 FDA approves Atezolizumab for BRAF V600 unresectable or metastatic melanoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-braf-v600-unresectable-or-metastatic-melanoma
    PubMed
  • 56 Nathan P, Dummer R, Long GV. et al. LBA43 – Spartalizumab plus Dabrafenib and Trametinib (Sparta-DabTram) in patients (pts) with previously untreated BRAF V600-mutant unresectable or metastatic melanoma: results from the randomized part 3 of the phase III COMBI-i trial. Ann Oncol 2020; 31 (Suppl. 04) S1172
    CrossrefPubMedSearch in Google Scholar
  • 57 A clinical trial of three study medicines (Encorafenib, Binimetinib, and Pembrolizumab) in patients with advanced or metastatic melanoma. https://clinicaltrials.gov/ct2/show/NCT04657991
    PubMed
  • 58 Zimmer L, Krackhardt A, Schultz ES. et al. Triplet therapy with Pembrolizumab (PEM), Encorafenib (ENC) and Binimetinib (BIN) in advanced, BRAF V600 mutant melanoma: Final results from the dose-finding phase I part of the IMMU-Target trial. Journal of Clinical Oncology 2021; 39: 9532
    CrossrefPubMedSearch in Google Scholar
  • 59 Pires da Silva I, Ahmed T, Reijers ILM. et al. Ipilimumab alone or Ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study. Lancet Oncol 2021; 22: 836-847
    CrossrefPubMedSearch in Google Scholar
  • 60 Preconditioning of tumor, tumor microenvironment and the immune system to immunotherapy (PROMIT). https://clinicaltrials.gov/ct2/show/NCT04225390
    PubMed
  • 61 Saiag P, Baghad B, Fort M. et al. Efficacy of hypofractionated radiotherapy (Rx) in melanoma patients who failed anti-PD-1 monotherapy: Assessing the abscopal effect. Journal of Clinical Oncology 2019; 37: 9537
    CrossrefPubMedSearch in Google Scholar
  • 62 Arance Fernandez AM, OʼDay SJ, de la Cruz Merino L. et al. Lenvatinib plus Pembrolizumab for advanced melanoma that progressed on a PD-1 or PD-L1 inhibitor: Initial results of LEAP-004. Ann Oncol 2020; 31 (Suppl. 04) S1173
    CrossrefPubMedSearch in Google Scholar
  • 63 Arance AM, de la Cruz Merino L, Petrella TM. et al. Lenvatinib plus Pembrolizumab for patients with advanced melanoma and confirmed progression on a PD-1 or PD-L1 inhibitor: Updated findings of LEAP-004. Journal of Clinical Oncology 2021; 39: 9504
    CrossrefPubMedSearch in Google Scholar
  • 64 Safety and efficacy study of Pembrolizumab (MK-3475) combined with Lenvatinib (MK-7902/E7080) as first-line intervention in adults with advance melanoma (MK-7902-003/E7080-G000-312/LEAP-003). https://clinicaltrials.gov/ct2/show/NCT03820986
    PubMed
  • 65 Lipson EJ, Tawbi HAH, Schadendorf D. et al. Relatlimab (RELA) plus Nivolumab (NIVO) versus NIVO in first-line advanced melanoma: primary phase III results from RELATIVITY-047 (CA224-047). Journal of Clinical Oncology 2021; 39: 9503
    CrossrefPubMedSearch in Google Scholar
  • 66 Hamid O, Wang D, Kim TM. et al. Clinical activity of Fianlimab (REGN3767), a human anti-LAG-3 monoclonal antibody, combined with Cemiplimab (anti-PD-1) in patients (pts) with advanced melanoma. Journal of Clinical Oncology 2021; 39: 9515
    CrossrefPubMedSearch in Google Scholar
  • 67 Study of efficacy and safety of novel Spartalizumab combinations in patients with previously treated unresectable or metastatic melanoma (PLATforM). https://clinicaltrials.gov/ct2/show/NCT03484923
    PubMed
  • 68 A study of NKTR-214 combined with Nivolumab vs Nivolumab alone in participants with previously untreated inoperable or metastatic melanoma. https://clinicaltrials.gov/ct2/show/NCT03635983
    PubMed
  • 69 Diab A, Tykodi SS, Daniels GA. et al. Bempegaldesleukin plus Nivolumab in first-line metastatic melanoma. Journal of Clinical Oncology 2021; 39: 2914-2925
    CrossrefPubMedSearch in Google Scholar
  • 70 4SC-202 in combination with Pembrolizumab in patients primary refractory/Non-responding to Prior Anti-PD-1 Therapy (SENSITIZE). https://clinicaltrials.gov/ct2/show/NCT03278665
    PubMed
  • 71 Evaluation of the safety and tolerability of i.v. administration of a cancer vaccine in patients with advanced melanoma (Lipo-MERIT). https://clinicaltrials.gov/ct2/show/NCT02410733
    PubMed
  • 72 Trial with BNT111 and Cemiplimab in combination or as single agents in patients with Anti-PD1-refractory/relapsed, unresectable Stage III or IV melanoma. https://clinicaltrials.gov/ct2/show/NCT04526899
    PubMed
  • 73 Study of RP1 monotherapy and RP1 in combination with Nivolumab (IGNYTE). https://clinicaltrials.gov/ct2/show/NCT03767348
    PubMed
  • 74 Efficacy, safety, and tolerability of V937 administered intravenously or intratumorally with Pembrolizumab (MK-3475) versus Pembrolizumab alone in participants with advanced/metastatic melanoma (V937-011). https://clinicaltrials.gov/ct2/show/NCT04152863
    PubMed
  • 75 A study of intratumoral/intralesional administration of V938 in combination with Pembrolizumab (MK-3475) in participants with advanced/metastatic or recurrent malignancies (V938-001). https://clinicaltrials.gov/ct2/show/NCT04135352
    PubMed
  • 76 A study of IMO-2125 in combination with Ipilimumab versus Ipilimumab alone in subjects with Anti-PD-1 refractory melanoma (ILLUMINATE-301) (ILLUMINATE-301). https://clinicaltrials.gov/ct2/show/NCT03445533
    PubMed