Malignant solid neoplasm, MSI-H or dMMR

4 regimens on this page 6 variants on this page

Note: this is a new type of page for HemOnc.org, as all other regimen pages (except for cancer of unknown primary) are tissue-specific. The initial drug with tissue-agnostic approval is for patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

All lines of therapy

Pembrolizumab monotherapy

Variant #1, q2wk dosing

Study	Evidence
Le et al. 2015 (KEYNOTE-016)	Phase II (RT)

Note: this was an expansion to a CRC-specific trial.

Biomarker eligibility criteria

• Protein: CD8 or PD-L1
• Alteration: expression
• Acceptable methods of measurement: IHC

Immunotherapy

• Pembrolizumab (Keytruda) 10 mg/kg IV once on day 1

14-day cycles

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.

Immunotherapy

• Pembrolizumab (Keytruda) 200 mg IV over 30 minutes once on day 1

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

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.

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

1. 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 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