Difference between revisions of "Malignant solid neoplasm, MSI-H or dMMR"

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m (Text replacement - "'''contains protocol'''" to "'''contains dosing details in abstract'''")
m (Text replacement - "'''contains dosing details in supplement'''" to "'''dosing details in supplement have been reviewed by our editors'''")
 
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{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
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=Guidelines=
 
=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==
 
==JSCO/ESMO/ASCO/JSMO/TOS==
 
*'''2020:''' Yoshino et al. [https://doi.org/10.1016/j.annonc.2020.03.299 JSCO—ESMO—ASCO—JSMO—TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions]
 
*'''2020:''' Yoshino et al. [https://doi.org/10.1016/j.annonc.2020.03.299 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=
 
=All lines of therapy=
 
==Dostarlimab monotherapy {{#subobject:ejg8a3|Regimen=1}}==
 
==Dostarlimab monotherapy {{#subobject:ejg8a3|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:5dnfj9|Variant=1}}===
 
===Regimen {{#subobject:5dnfj9|Variant=1}}===
 
{| class="wikitable sortable" style="color:white; background-color:#404040"
 
{| class="wikitable sortable" style="color:white; background-color:#404040"
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{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
−
!style="width: 33%"|Years of enrollment
+
!style="width: 33%"|Dates of enrollment
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8739161/ Patnaik et al. 2021 (GARNET)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8739161/ Patnaik et al. 2021 (GARNET<sub>MSI-H</sub>)]
 
|2017-2019
 
|2017-2019
 
| style="background-color:#91cf61" |Phase 1 (RT)
 
| style="background-color:#91cf61" |Phase 1 (RT)
 
|-
 
|-
 
|}
 
|}
−
''Note: dosing is as provided in the FDA release.''
+
''Note: this was the recommended therapeutic dose.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
 
*[[Dostarlimab (Jemperli)]] as follows:
 
*[[Dostarlimab (Jemperli)]] as follows:
 
**Cycles 1 to 4: 500 mg IV over 30 minutes once on day 1
 
**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
 
**Cycle 5 onwards: 1000 mg IV over 30 minutes once on day 1
−
 
 
'''21-day cycle for 4 cycles, then 42-day cycles'''
 
'''21-day cycle for 4 cycles, then 42-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''GARNET<sub>MSI-H</sub>:''' 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. [https://doi.org/10.1007/s00280-021-04358-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8739161/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34750637/ PubMed] [https://clinicaltrials.gov/study/NCT02715284 NCT02715284]
  
 +
==Envafolimab monotherapy {{#subobject:euj7a3|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1dcfj9|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8218452/ Li et al. 2021 (KN035-CN-006)]
 +
|2018-2019
 +
| style="background-color:#91cf61" |Phase 2
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Envafolimab (Enweida)]] 150 mg SC once on day 1
 +
'''7-day cycles'''
 +
</div></div>
 
===References===
 
===References===
−
#'''GARNET:''' 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. [https://doi.org/10.1007/s00280-021-04358-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8739161/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34750637/ PubMed] NCT02715284
+
#'''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. [https://doi.org/10.1186/s13045-021-01095-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8218452/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34154614/ PubMed] [https://clinicaltrials.gov/study/NCT03667170 NCT03667170]
  
 
==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}==
 
==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #1, q2wk dosing {{#subobject:87f9c7|Variant=1}}===
 
===Regimen variant #1, q2wk dosing {{#subobject:87f9c7|Variant=1}}===
 
{| class="wikitable" style="width: 60%; text-align:center;"  
 
{| class="wikitable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
−
!style="width: 33%"|Years of enrollment
+
!style="width: 33%"|Dates of enrollment
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481136/ Le et al. 2015 (KEYNOTE-016)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481136/ Le et al. 2015 (KEYNOTE-016)]
−
|2013-2015
+
|2013-09 to 2016-09
 
|style="background-color:#91cf61"|Phase 2 (RT)
 
|style="background-color:#91cf61"|Phase 2 (RT)
 
|-
 
|-
 
|}
 
|}
 
''Note: this was an expansion to a CRC-specific trial.''
 
''Note: this was an expansion to a CRC-specific trial.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*Protein: MMR
 
*Protein: MMR
 
*Alteration: [[Biomarkers#dMMR|dMMR]]
 
*Alteration: [[Biomarkers#dMMR|dMMR]]
−
 
+
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
 
*[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1
 
*[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1
−
 
 
'''14-day cycles'''
 
'''14-day cycles'''
−
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #2, q3wk, adult dosing {{#subobject:7b36e9|Variant=1}}===
 
===Regimen variant #2, q3wk, adult dosing {{#subobject:7b36e9|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
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{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
−
!style="width: 33%"|Years of enrollment
+
!style="width: 33%"|Dates of enrollment
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
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|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8184060/ Marabelle et al. 2019 (KEYNOTE-158)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8184060/ Marabelle et al. 2019 (KEYNOTE-158)]
 +
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 +
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-294-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
 +
|-
 +
|} -->
 
|2016-2018
 
|2016-2018
 
|style="background-color:#91cf61"|Phase 2 (RT)
 
|style="background-color:#91cf61"|Phase 2 (RT)
Line 85: Line 112:
 
|}
 
|}
 
''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.''
 
''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.''
−
 
+
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*''KEYNOTE-164''
 
*''KEYNOTE-164''
Line 95: Line 122:
 
**Alteration: [[Biomarkers#Expression|expression]]
 
**Alteration: [[Biomarkers#Expression|expression]]
 
**Acceptable methods of measurement: IHC
 
**Acceptable methods of measurement: IHC
−
 
+
====Prior treatment criteria====
−
====Preceding treatment====
+
*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
−
*''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
+
</div>
−
 
+
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
 
*[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1
 
*[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1
−
 
 
'''21-day cycle for up to 35 cycles (2 years)'''
 
'''21-day cycle for up to 35 cycles (2 years)'''
−
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #3, q3wk, pediatric dosing {{#subobject:392a4b|Variant=1}}===
 
===Regimen variant #3, q3wk, pediatric dosing {{#subobject:392a4b|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
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{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
−
!style="width: 33%"|Years of enrollment
+
!style="width: 33%"|Dates of enrollment
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
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|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8184060/ Marabelle et al. 2019 (KEYNOTE-158)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8184060/ Marabelle et al. 2019 (KEYNOTE-158)]
 +
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 +
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-294-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
 +
|-
 +
|} -->
 
|2016-2018
 
|2016-2018
 
|style="background-color:#91cf61"|Phase 2 (RT)
 
|style="background-color:#91cf61"|Phase 2 (RT)
Line 124: Line 155:
 
|}
 
|}
 
''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.''
 
''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.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*''KEYNOTE-164''
 
*''KEYNOTE-164''
Line 133: Line 165:
 
**Alteration: [[Biomarkers#Expression|expression]]
 
**Alteration: [[Biomarkers#Expression|expression]]
 
**Acceptable methods of measurement: IHC
 
**Acceptable methods of measurement: IHC
−
 
+
====Prior treatment criteria====
−
====Preceding treatment====
+
*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
−
*''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
+
</div>
−
 
+
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
 
*[[Pembrolizumab (Keytruda)]] 2 mg/kg (maximum dose of 200 mg) IV over 30 minutes once on day 1  
 
*[[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)'''
 
'''21-day cycle for up to 35 cycles (2 years)'''
−
 
+
</div></div>
 
===References===
 
===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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1500596 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481136/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26028255 PubMed] NCT01876511
+
# '''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. [https://doi.org/10.1056/NEJMoa1500596 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481136/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26028255/ PubMed] [https://clinicaltrials.gov/study/NCT01876511 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. [http://science.sciencemag.org/content/357/6349/409.long link to original article]  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576142/ link to PMC article] '''contains verified protocol in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28596308 PubMed]
+
## '''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. [https://doi.org/10.1126/science.aan6733 link to original article]  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576142/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28596308/ PubMed]
 
<!-- #'''Abstract:''' Dung T. Le, Takayuki Yoshino, Dirk Jäger, Thierry Andre, Johanna C. Bendell, Ruixue Wang... SoonMo Peter Kang, Minori Koshiji, Luis A. Diaz. KEYNOTE-164: Phase II study of pembrolizumab (MK-3475) for patients with previously treated, microsatellite instability-high advanced colorectal carcinoma. J Clin Oncol [https://doi.org/10.1200/jco.2016.34.4_suppl.tps787 abstract TPS787] and [https://doi.org/10.1200/JCO.2016.34.15_suppl.TPS3631 abstract TPS3631] -->
 
<!-- #'''Abstract:''' Dung T. Le, Takayuki Yoshino, Dirk Jäger, Thierry Andre, Johanna C. Bendell, Ruixue Wang... SoonMo Peter Kang, Minori Koshiji, Luis A. Diaz. KEYNOTE-164: Phase II study of pembrolizumab (MK-3475) for patients with previously treated, microsatellite instability-high advanced colorectal carcinoma. J Clin Oncol [https://doi.org/10.1200/jco.2016.34.4_suppl.tps787 abstract TPS787] and [https://doi.org/10.1200/JCO.2016.34.15_suppl.TPS3631 abstract TPS3631] -->
−
#'''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. [https://doi.org/10.1200/jco.19.02107 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7031958/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31725351/ PubMed] NCT02460198
+
#'''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. [https://doi.org/10.1200/jco.19.02107 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7031958/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31725351/ PubMed] [https://clinicaltrials.gov/study/NCT02460198 NCT02460198]
 
<!-- # '''Abstract:''' Jan H.M. Schellens, Aurelien Marabelle, Susan Zeigenfuss, Jie Ding, Scott Knowles Pruitt, and Hyun Cheol Chung. Pembrolizumab for previously treated advanced cervical squamous cell cancer: Preliminary results from the phase 2 KEYNOTE-158 study. Journal of Clinical Oncology 35, no. 15_suppl (May 20 2017) 5514-5514. [https://doi.org/10.1200/JCO.2017.35.15_suppl.5514 link to abstract] -->
 
<!-- # '''Abstract:''' Jan H.M. Schellens, Aurelien Marabelle, Susan Zeigenfuss, Jie Ding, Scott Knowles Pruitt, and Hyun Cheol Chung. Pembrolizumab for previously treated advanced cervical squamous cell cancer: Preliminary results from the phase 2 KEYNOTE-158 study. Journal of Clinical Oncology 35, no. 15_suppl (May 20 2017) 5514-5514. [https://doi.org/10.1200/JCO.2017.35.15_suppl.5514 link to abstract] -->
−
# '''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. [https://doi.org/10.1200/jco.19.02105 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8184060/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31682550 PubMed] NCT02628067
+
# '''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. [https://doi.org/10.1200/jco.19.02105 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8184060/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31682550/ PubMed] [https://clinicaltrials.gov/study/NCT02628067 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. [https://doi.org/10.1016/j.annonc.2022.05.519 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35680043/ PubMed]
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==Serplulimab monotherapy {{#subobject:eusea3|Regimen=1}}==
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<div class="toccolours" style="background-color:#eeeeee">
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===Regimen {{#subobject:serfj9|Variant=1}}===
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{| class="wikitable sortable" style="width: 60%; text-align:center;"
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!style="width: 33%"|Study
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!style="width: 33%"|Dates of enrollment
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!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
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|-
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9726893/ Qin et al. 2022 (HLX10-010-MSI201)]
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|2019-07-22 to 2021-01-09
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| style="background-color:#91cf61" |Phase 2 (RT)
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|-
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|}
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<div class="toccolours" style="background-color:#b3e2cd">
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====Immunotherapy====
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*[[Serplulimab (Hansizhuang)]] 3 mg/kg IV once on day 1
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'''14-day cycle for up to 52 cycles (2 years)'''
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</div></div>
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===References===
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#'''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. [https://doi.org/10.1038/s41416-022-02001-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9726893/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36261583/ PubMed] [https://clinicaltrials.gov/study/NCT03941574 NCT03941574]
  
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[[Category:MSI-H or dMMR regimens]]
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[[Category:Malignant solid neoplasm, MSI-H or dMMR regimens]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Malignant solid neoplasm]]
 
[[Category:Malignant solid neoplasm]]
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[[Category:Site-agnostic regimens]]
 

Latest revision as of 17:12, 17 July 2024

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4 regimens on this page
6 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

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

  1. 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 PubMed NCT02715284

Envafolimab monotherapy

Regimen

Study Dates of enrollment Evidence
Li et al. 2021 (KN035-CN-006) 2018-2019 Phase 2

Immunotherapy

7-day cycles

References

  1. 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 PubMed 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

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

21-day cycle for up to 35 cycles (2 years)


Regimen variant #3, q3wk, pediatric 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 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

21-day cycle for up to 35 cycles (2 years)

References

  1. 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 abstract have been reviewed by our editors link to PMC article PubMed NCT01876511
    1. 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 dosing details in supplement have been reviewed by our editors PubMed
  2. 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 PubMed NCT02460198
  3. 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 PubMed NCT02628067
    1. 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 PubMed

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

14-day cycle for up to 52 cycles (2 years)

References

  1. 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 PubMed NCT03941574
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