Malignant solid neoplasm, MSI-H or dMMR

Back to Top
Last updated on 2024-12-02:4 regimens on this page
7 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==JSCO/ESMO/ASCO/JSMO/TOS==
*2020: Yoshino et al. JSCO—ESMO—ASCO—JSMO—TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions
=All lines of therapy=
==Dostarlimab monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence
Patnaik et al. 2021 (GARNETMSI-H)	2017-2019 	Phase 1 (RT)
Note: this was the recommended therapeutic dose.
====Immunotherapy====
*Dostarlimab (Jemperli) as follows:
**Cycles 1 to 4: 500 mg IV over 30 minutes once on day 1
**Cycle 5 onwards: 1000 mg IV over 30 minutes once on day 1
21-day cycle for 4 cycles, then 42-day cycles
===References===
#GARNETMSI-H: Patnaik A, Weiss GJ, Rasco DW, Blaydorn L, Mirabella A, Beeram M, Guo W, Lu S, Danaee H, McEachern K, Im E, Sachdev JC. Safety, antitumor activity, and pharmacokinetics of dostarlimab, an anti-PD-1, in patients with advanced solid tumors: a dose-escalation phase 1 trial. Cancer Chemother Pharmacol. 2022 Jan;89(1):93-103. Epub 2021 Nov 8. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02715284
==Envafolimab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Li et al. 2021 (KN035-CN-006)	2018-2019 	Phase 2
====Immunotherapy====
*Envafolimab (Enweida) 150 mg SC once on day 1
7-day cycles
===References===
#KN035-CN-006: Li J, Deng Y, Zhang W, Zhou AP, Guo W, Yang J, Yuan Y, Zhu L, Qin S, Xiang S, Lu H, Gong J, Xu T, Liu D, Shen L. Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair/microsatellite instability high solid tumors. J Hematol Oncol. 2021 Jun 21;14(1):95. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT03667170
==Pembrolizumab monotherapy==
===Regimen variant #1, q2wk dosing===
Study 	Dates of enrollment	Evidence
Le et al. 2015 (KEYNOTE-016)	2013-09 to 2016-09 	Phase 2 (RT)
Note: this was an expansion to a CRC-specific trial.
====Biomarker eligibility criteria====
*Protein: MMR
*Alteration: dMMR
====Immunotherapy====
*Pembrolizumab (Keytruda) 10 mg/kg IV over 30 minutes once on day 1
14-day cycles
===Regimen variant #2, q3wk, adult dosing===
FDA-recommended dose
Study 	Dates of enrollment	Evidence
Le et al. 2019 (KEYNOTE-164) 	2015-2017 	Phase 2 (RT)
Marabelle et al. 2019 (KEYNOTE-158)	2016-2018 	Phase 2 (RT)
Note: this is the FDA-approved adult pembrolizumab dose and schedule based on a pooled analysis of 5 non-randomized trials, of which two were prospective: KEYNOTE-158 and KEYNOTE-164.
====Biomarker eligibility criteria====
*KEYNOTE-164
**Protein: MMR
**Alteration: dMMR
**Acceptable methods of measurement: IHC
*KEYNOTE-158
**Protein: PD-L1
**Alteration: expression
**Acceptable methods of measurement: IHC
====Prior treatment criteria====
*KEYNOTE-164: prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and, if KRAS and NRAS wild type, cetuximab or panitumumab; no prior anti-cancer therapy within last 2 weeks
====Immunotherapy====
*Pembrolizumab (Keytruda) 200 mg IV over 30 minutes once on day 1
21-day cycle for up to 35 cycles (2 years)
===Regimen variant #3, q3wk, pediatric dosing without cap===
Study 	Dates of enrollment 	Evidence
Geoerger et al. 2019 (KEYNOTE-051)	2015-03-23 to 2018-09-03	Phase 1/2 (RT)
====Immunotherapy====
*Pembrolizumab (Keytruda) 2 mg/kg IV once on day 1 
21-day cycle for up to 35 cycles (2 years)
===Regimen variant #4, q3wk, pediatric dosing with cap===
FDA-recommended dose
Study 	Dates of enrollment	Evidence
Le et al. 2019 (KEYNOTE-164) 	2015-2017 	Phase 2 (RT)
Marabelle et al. 2019 (KEYNOTE-158)	2016-2018 	Phase 2 (RT)
Note: this is the FDA-approved pediatric pembrolizumab dose and schedule based on a pooled analysis of 5 non-randomized trials, of which two were prospective: KEYNOTE-158 and KEYNOTE-164.
====Biomarker eligibility criteria====
*KEYNOTE-164
**Protein: MMR
**Alteration: dMMR
**Acceptable methods of measurement: IHC
*KEYNOTE-158
**Protein: PD-L1
**Alteration: expression
**Acceptable methods of measurement: IHC
====Prior treatment criteria====
*KEYNOTE-164: prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and, if KRAS and NRAS wild type, cetuximab or panitumumab; no prior anti-cancer therapy within last 2 weeks
====Immunotherapy====
*Pembrolizumab (Keytruda) 2 mg/kg (maximum dose of 200 mg) IV over 30 minutes once on day 1 
21-day cycle for up to 35 cycles (2 years)
===References===
# KEYNOTE-016: Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. Epub 2015 May 30. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT01876511
## Update: Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8. link to original article link to PMC article EuroPMC
#KEYNOTE-164: Le DT, Kim TW, Van Cutsem E, Geva R, Jäger D, Hara H, Burge M, O'Neil B, Kavan P, Yoshino T, Guimbaud R, Taniguchi H, Elez E, Al-Batran SE, Boland PM, Crocenzi T, Atreya CE, Cui Y, Dai T, Marinello P, Diaz LA Jr, André T. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164. J Clin Oncol. 2020 Jan 1;38(1):11-19. Epub 2019 Nov 14. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02460198
# KEYNOTE-158: Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, Geva R, Gottfried M, Penel N, Hansen AR, Piha-Paul SA, Doi T, Gao B, Chung HC, Lopez-Martin J, Bang YJ, Frommer RS, Shah M, Ghori R, Joe AK, Pruitt SK, Diaz LA Jr. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020 Jan 1;38(1):1-10. Epub 2019 Nov 4. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02628067
##Update: Maio M, Ascierto PA, Manzyuk L, Motola-Kuba D, Penel N, Cassier PA, Bariani GM, De Jesus Acosta A, Doi T, Longo F, Miller WH, Oh DY, Gottfried M, Xu L, Jin F, Norwood K, Marabelle A. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Ann Oncol. 2022 Sep;33(9):929-938. Epub 2022 Jun 6. link to original article EuroPMC
# KEYNOTE-051: Geoerger B, Kang HJ, Yalon-Oren M, Marshall LV, Vezina C, Pappo A, Laetsch TW, Petrilli AS, Ebinger M, Toporski J, Glade-Bender J, Nicholls W, Fox E, DuBois SG, Macy ME, Cohn SL, Pathiraja K, Diede SJ, Ebbinghaus S, Pinto N. Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2020 Jan;21(1):121-133. Epub 2019 Dec 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02332668
==Serplulimab monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Qin et al. 2022 (HLX10-010-MSI201)	2019-07-22 to 2021-01-09	Phase 2 (RT)
====Immunotherapy====
*Serplulimab (Hansizhuang) 3 mg/kg IV once on day 1
14-day cycle for up to 52 cycles (2 years)
===References===
#HLX10-010-MSI201: Qin S, Li J, Zhong H, Jin C, Chen L, Yuan X, Fan Q, Chen K, Cao P, Xiao J, Jiang D, Zhang T, Zhang H, Wang X, Wang W, Han L, Wang Q, Zhu J; Serplulimab-MSI-H Investigators. Serplulimab, a novel anti-PD-1 antibody, in patients with microsatellite instability-high solid tumours: an open-label, single-arm, multicentre, phase II trial. Br J Cancer. 2022 Dec;127(12):2241-2248. Epub 2022 Oct 19. Erratum in: Br J Cancer. 2022 Nov 2. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03941574
Category:Malignant solid neoplasm, MSI-H or dMMR regimens
Category:Biomarker-specific pages
Category:Malignant solid neoplasm