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Proffered Paper session - Translational research

1758O - Neoadjuvant pembrolizumab in localized/locally advanced solid tumors with mismatch repair deficiency


19 Sep 2021


Proffered Paper session - Translational research


Kaysia Ludford


Annals of Oncology (2021) 32 (suppl_5): S1211-S1226. 10.1016/annonc/annonc716


K. Ludford1, K. Raghav1, M.A. Blum Murphy1, N.D. Fleming2, D. Nelson1, M.S. Lee1, B.G. Smaglo1, Y.N. You3, M.M. Tillman4, C. Kamiya-matsuoka5, S. Thirumurthi6, C. Messick4, B. Johnson1, E. Vilar7, J. Thomas1, W.C. Foo8, W. Qiao9, S. Kopetz1, M.J. Overman1

Author affiliations

  • 1 Gastrointestinal Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
  • 2 Gynecologic Oncology And Reproductive Medicine, MD Anderson Cancer Center, 77030 - Houston/US
  • 3 Colon And Rectal Surgery, MD Anderson Cancer Center, 77030 - Houston/US
  • 4 Surgical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
  • 5 Neuro-oncology, The University of Texas M. D. Anderson Cancer Center, 77030 - Houston/US
  • 6 Gastroenterology, Hepatology And Nutrition, MD Anderson Cancer Center, 77030 - Houston/US
  • 7 Clinical Cancer Prevention, MD Anderson Cancer Center, 77030 - Houston/US
  • 8 Pathology, Anatomical, MD Anderson Cancer Center, 77030 - Houston/US
  • 9 Biostatistics, MD Anderson Cancer Center, 77030 - Houston/US


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Abstract 1758O


Pembrolizumab (pembro) significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors. This study evaluates pembro in the neoadjuvant space with the potential for an organ-sparing approach.


This is a phase 2 open-label, single center trial of MSI-H/dMMR non-metastatic solid tumors with localized unresectable or high risk resectable (defined as ≥ 20% recurrence) with measurable disease. Treatment is Pembro 200mg every 3 wks for 8 cycles followed by surgical resection with option to continue therapy for 18 cycles followed by observation. First restaging is at 6 wks and includes baseline and 3-week 70-gene ctDNA assessment. To continue on study, patients are required to have PR/CR, SD with tumor shrinkage or SD with decline in ctDNA. The co-primary endpoints are safety and pathological complete response (pCR). Key secondary endpoints are response rate and organ-sparing at one year for patients who declined surgery.


Between 10/2019 and 3/2021, 35 pts were enrolled and study has completed enrollment. Tumor types included 27 CRC and 8 non-CRC: endometrial, gastric, meningioma, 2 duodenal, ampullary and 2 pancreatic. Median follow-up was 9 months (range 0.1 - 17). Among 32 evaluable pts, best ORR was 75% (CR 25% , PR 50%), SD 22% and PD 3%. Luminal endoscopic response was seen in 17/19 (89%) pts. Among 8 (23%) pts who underwent surgery, pCR was seen in 4. At present non-operative approach was chosen by 8 (23%) pts with 1-year organ-sparing seen in 2/2 evaluable pts. Treatment-related grade 3/4 immune adverse events were seen in 3 (9%) pts (transaminitis, diarrhea and type 1 diabetes). Baseline ctDNA mutations were present in 20 (57%) pts and at 3 weeks declined in 15 (75%), unchanged in 1, no paired 3 week sample in 1, and increased in 3. Tumor microenvironment immune analysis is ongoing and will be presented.


Neoadjuvant pembrolizumab in dMMR/MSI-H cancers is safe and resulted in high rates of radiographic and endoscopic response which has implications for organ-sparing strategies. Non-operative management of dMMR/MSI-H localized solid tumors should be further investigated.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

The authors.




All authors have declared no conflicts of interest.

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