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MSI-H or dMMR

1 regimens on this page
3 variants on this page


Contents

All lines of therapy

Pembrolizumab monotherapy

Regimen variant #1, q2wk dosing

Study Years of enrollment Evidence
Le et al. 2015 (KEYNOTE-016) 2013-2015 Phase II (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 Evidence
Le et al. 2016 (KEYNOTE-164) Phase II
Schellens et al. 2017 (KEYNOTE-158) Phase II

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

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

Immunotherapy

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

Regimen variant #3, q3wk, pediatric dosing

FDA-recommended dose
Study Evidence
Le et al. 2016 (KEYNOTE-164) Phase II
Schellens et al. 2017 (KEYNOTE-158) Phase II

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

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

Immunotherapy

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

References

  1. Abstract: Dung T. Le, Takayuki Yoshino, Dirk J├Ąger, 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 abstract TPS787 and abstract TPS3631; NCT02460198 at ClinicalTrials.gov
  2. 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. link to abstract
  3. 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 contains protocol link to PMC article PubMed
    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 contains verified protocol in supplement PubMed