Uveal melanoma

Section editor transclusions Note: this page is for regimens specific to uveal melanoma; see the main melanoma page for other regimens.

13 regimens on this page 13 variants on this page

Guidelines

NCCN

• NCCN Guidelines - Uveal Melanoma

Metastatic or unresectable disease

Dacarbazine monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Carvajal et al. 2014 (MSK 10-053)	2010-2013	Randomized Phase II (C)	Selumetinib	Might have inferior OS
Carvajal et al. 2018 (SUMIT)	2014-2015	Phase III (C)	Dacarbazine & Selumetinib	Did not meet primary endpoint of PFS
Nathan et al. 2021 (IMCgp100-202)	2017-2020	Phase III (C)	Tebentafusp	Inferior OS

Chemotherapy

• Dacarbazine (DTIC) 1000 mg/m² IV once on day 1

21-day cycles

References

1. MSK 10-053: Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Doyle A, Ancell K, Panageas KS, Bluth M, Hedvat C, Erinjeri J, Ambrosini G, Marr B, Abramson DH, Dickson MA, Wolchok JD, Chapman PB, Schwartz GK. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014 Jun 18;311(23):2397-405. link to original article link to PMC article PubMed NCT01143402
2. SUMIT: Carvajal RD, Piperno-Neumann S, Kapiteijn E, Chapman PB, Frank S, Joshua AM, Piulats JM, Wolter P, Cocquyt V, Chmielowski B, Evans TRJ, Gastaud L, Linette G, Berking C, Schachter J, Rodrigues MJ, Shoushtari AN, Clemett D, Ghiorghiu D, Mariani G, Spratt S, Lovick S, Barker P, Kilgour E, Lai Z, Schwartz GK, Nathan P. Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: a phase III, multicenter, randomized trial (SUMIT). J Clin Oncol. 2018 Apr 20;36(12):1232-1239. Epub 2018 Mar 12. link to original article contains verified protocol PubMed NCT01974752
3. IMCgp100-202: Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM, Joshua AM, Sacco JJ, Shoushtari AN, Orloff M, Piulats JM, Milhem M, Salama AKS, Curti B, Demidov L, Gastaud L, Mauch C, Yushak M, Carvajal RD, Hamid O, Abdullah SE, Holland C, Goodall H, Piperno-Neumann S; IMCgp100-202 Investigators. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196-1206. link to original article contains verified protocol PubMed NCT03070392

Fotemustine monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Leyvraz et al. 2014 (EORTC 18021)	2005-2011	Phase 3 (C)	Fotemustine; HAI	Did not meet primary endpoint of OS

Chemotherapy

• Fotemustine (Muphoran) as follows:
  • Weeks 1 to 3: 100 mg/m² IV once per day on days 1, 8, 15
  • Weeks 4 to 8: no treatment
  • Week 9 onwards: 100 mg/m² IV once on day 1, every 3 weeks

8-week induction cycle, then 21-day cycles

References

1. EORTC 18021: Leyvraz S, Piperno-Neumann S, Suciu S, Baurain JF, Zdzienicki M, Testori A, Marshall E, Scheulen M, Jouary T, Negrier S, Vermorken JB, Kaempgen E, Durando X, Schadendorf D, Karra Gurunath R, Keilholz U. Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. Ann Oncol. 2014 Mar;25(3):742-6. Epub 2014 Feb 7. link to original article link to PMC article contains protocol PubMed NCT00110123

Ipilimumab monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Nathan et al. 2021 (IMCgp100-202)	2017-2020	Phase III (C)	Tebentafusp	Inferior OS

Immunotherapy

• Ipilimumab (Yervoy) 3 mg/kg IV once on day 1

21-day cycle for up to 4 cycles

References

1. IMCgp100-202: Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM, Joshua AM, Sacco JJ, Shoushtari AN, Orloff M, Piulats JM, Milhem M, Salama AKS, Curti B, Demidov L, Gastaud L, Mauch C, Yushak M, Carvajal RD, Hamid O, Abdullah SE, Holland C, Goodall H, Piperno-Neumann S; IMCgp100-202 Investigators. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196-1206. link to original article contains verified protocol PubMed NCT03070392

Ipilimumab & Nivolumab

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Regimen variant #1, "NIVO1+IPI3", flat-dose maintenance

Study	Evidence
Piulats et al. 2021 (GEM-1402)	Phase II

Immunotherapy

• Ipilimumab (Yervoy) as follows:
  • Cycles 1 to 4: 3 mg/kg IV once on day 1
• Nivolumab (Opdivo) as follows:
  • Cycles 1 to 4: 1 mg/kg IV once on day 1
  • Cycle 5 onwards: 3 mg/kg IV once on day 1

21-day cycle for 4 cycles, then 14-day cycles

Regimen variant #2, "NIVO3+IPI1", flat-dose maintenance

Study	Evidence
Pelster et al. 2020	Phase II

Immunotherapy

• Ipilimumab (Yervoy) as follows:
  • Cycles 1 to 4: 1 mg/kg IV once on day 1
• Nivolumab (Opdivo) as follows:
  • Cycles 1 to 4: 3 mg/kg IV once on day 1
  • Cycle 5 onwards: 480 mg IV once on day 1

21-day cycle for 4 cycles, then 28-day cycles

References

1. GEM-1402: Piulats JM, Espinosa E, de la Cruz Merino L, Varela M, Alonso Carrión L, Martín-Algarra S, López Castro R, Curiel T, Rodríguez-Abreu D, Redrado M, Gomà M, Rullán AJ, Calvo González A, Berrocal-Jaime A. Nivolumab Plus Ipilimumab for Treatment-Naïve Metastatic Uveal Melanoma: An Open-Label, Multicenter, Phase II Trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402). J Clin Oncol. 2021 Feb 20;39(6):586-598. link to original article PubMed NCT02626962

1. Pelster MS, Gruschkus SK, Bassett R, Gombos DS, Shephard M, Posada L, Glover MS, Simien R, Diab A, Hwu P, Carter BW, Patel SP. Nivolumab and Ipilimumab in Metastatic Uveal Melanoma: Results From a Single-Arm Phase II Study. J Clin Oncol. 2021 Feb 20;39(6):599-607. doi: 10.1200/JCO.20.00605. Epub 2020 Oct 30. link to original article PubMed NCT01585194

Pembrolizumab monotherapy

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Regimen variant #1, weight-based

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Nathan et al. 2021 (IMCgp100-202)	2017-2020	Phase III (C)	Tebentafusp	Inferior OS

Immunotherapy

• Pembrolizumab (Keytruda) 2 mg/kg (maximum dose of 200 mg) IV once on day 1

21-day cycles

Regimen variant #2, flat dosing

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Nathan et al. 2021 (IMCgp100-202)	2017-2020	Phase III (C)	Tebentafusp	Inferior OS

Immunotherapy

• Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycles

References

1. IMCgp100-202: Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM, Joshua AM, Sacco JJ, Shoushtari AN, Orloff M, Piulats JM, Milhem M, Salama AKS, Curti B, Demidov L, Gastaud L, Mauch C, Yushak M, Carvajal RD, Hamid O, Abdullah SE, Holland C, Goodall H, Piperno-Neumann S; IMCgp100-202 Investigators. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196-1206. link to original article contains verified protocol PubMed NCT03070392

TACE monotherapy

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TACE: Trans-Arterial Chemo-Embolization

Regimen

Study	Evidence
Mavligit et al. 1988	Non-randomized

Chemotherapy

• TACE

1 or more treatments

References

1. Mavligit GM, Charnsangavej C, Carrasco CH, Patt YZ, Benjamin RS, Wallace S. Regression of ocular melanoma metastatic to the liver after hepatic arterial chemoembolization with cisplatin and polyvinyl sponge. JAMA. 1988 Aug 19;260(7):974-6. link to original article PubMed

Selumetinib monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Carvajal et al. 2014 (MSK 10-053)	2010-2013	Randomized Phase II (E-switch-ooc)	1. Dacarbazine 2. Temozolomide	Might have superior OS

Targeted therapy

• Selumetinib (Koselugo) 75 mg PO twice per day

Continued indefinitely

References

1. MSK 10-053: Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Doyle A, Ancell K, Panageas KS, Bluth M, Hedvat C, Erinjeri J, Ambrosini G, Marr B, Abramson DH, Dickson MA, Wolchok JD, Chapman PB, Schwartz GK. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014 Jun 18;311(23):2397-405. link to original article link to PMC article contains verified protocol PubMed NCT01143402

Tebentafusp monotherapy

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Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Nathan et al. 2021 (IMCgp100-202)	2017-2020	Phase 3 (E-RT-switch-ooc)	Investigator's choice of: 1. Dacarbazine 2. Ipilimumab 3. Pembrolizumab	Superior OS OS12: 73% vs 59% (HR 0.51, 95% CI 0.37-0.71)

Immunotherapy

• Tebentafusp (Kimmtrak) as follows:
  • Cycle 1: 20 mcg IV once on day 1
  • Cycle 2: 30 mcg IV once on day 1
  • Cycle 3 onwards: 68 mcg IV once on day 1

7-day cycles

References

1. IMCgp100-202: Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM, Joshua AM, Sacco JJ, Shoushtari AN, Orloff M, Piulats JM, Milhem M, Salama AKS, Curti B, Demidov L, Gastaud L, Mauch C, Yushak M, Carvajal RD, Hamid O, Abdullah SE, Holland C, Goodall H, Piperno-Neumann S; IMCgp100-202 Investigators. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196-1206. link to original article contains verified protocol PubMed NCT03070392

Temozolomide monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Carvajal et al. 2014 (MSK 10-053)	2010-2013	Randomized Phase II (C)	Selumetinib	Might have inferior OS

Chemotherapy

• Temozolomide (Temodar) 150 mg/m² PO once per day on days 1 to 5

28-day cycles

References

1. MSK 10-053: Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Doyle A, Ancell K, Panageas KS, Bluth M, Hedvat C, Erinjeri J, Ambrosini G, Marr B, Abramson DH, Dickson MA, Wolchok JD, Chapman PB, Schwartz GK. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014 Jun 18;311(23):2397-405. link to original article link to PMC article contains protocol PubMed NCT01143402

TILs

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TILs: Tumor Ifiltrating Lymphocytes

Regimen

Study	Evidence
Chandran et al. 2017 (NCI 13-C-0093)	Phase II

Preceding treatment

• FC lymphodepletion

Immunotherapy

• Autologous TILs

References

1. NCI 13-C-0093: Chandran SS, Somerville RPT, Yang JC, Sherry RM, Klebanoff CA, Goff SL, Wunderlich JR, Danforth DN, Zlott D, Paria BC, Sabesan AC, Srivastava AK, Xi L, Pham TH, Raffeld M, White DE, Toomey MA, Rosenberg SA, Kammula US. Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study. Lancet Oncol. 2017 Jun;18(6):792-802. Epub 2017 Apr 7. link to original article link to PMC article PubMed NCT01814046