Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper session - Translational research

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

Date

19 Sep 2021

Session

Proffered Paper session - Translational research

Presenters

Kaysia Ludford

Citation

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

Authors

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
More

Resources

Login to access the resources on OncologyPRO.

Abstract 1758O

Background

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.

Methods

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.

Results

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.

Conclusions

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

NCT04082572.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Merck.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.