100% Complete Response Rate in 14 Patients With Rectal Cancer Treated With Neoadjuvant Dostarlimab-gxly

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In a study of 18 patients with locally advanced mismatch repair–deficient (dMMR) rectal cancer, 6 months of neoadjuvant treatment with the anti–PD-1 agent dostarlimab-gxly alone led to clinical complete responses in 100% of the study’s first 14 patients.1 These results were presented at the 2022 ASCO Annual Meeting by Andrea Cercek, MD, Head of the Colorectal Cancer Section and Co-Director of the Center for Young Onset Colorectal and Gastrointestinal Cancers at Memorial Sloan Kettering Cancer Center, New York. The study findings were simultaneously published in The New England Journal of Medicine.2

Andrea Cercek, MD

Andrea Cercek, MD

“We were obviously beyond thrilled with the results,” Dr. Cercek commented. “We’ve now treated a total of 14 patients, and all have had a clinical complete response to dostarlimab alone…. No patients have required chemotherapy, radiation therapy, or surgery. There were no grade 3 or 4 events. There have been no disease recurrences observed…, although longer follow-up is certainly required to establish the durability of this treatment.”

Median follow-up is currently just 6.8 months. However, four patients have been followed for close to 2 years and four have received less than 6 months of the required treatment. 

About the Study 

The single-arm phase II study will ultimately enroll 30 patients with newly diagnosed clinical stage II and III dMMR rectal cancer. To date, all but 1 of 18 patients has had node-positive disease, and about half have Lynch syndrome. Most (78%) have T3 or T4 rectal tumors. The median patient age is 54 (range, 26–78 years). All patients had dMMR rectal cancers and all had wild-type BRAF V600F; the mean tumor mutational burden was 67.

“I’d like to highlight that the majority of these patients had big bulky tumors, and 94% had node-positive disease,” Dr. Cercek said. 

Patients received dostarlimab at 500 mg intravenously every 3 weeks for 6 months and then underwent radiologic and endoscopic evaluations. The protocol called for patients with clinical complete responses to be followed nonoperatively every 4 months; those with residual disease would undergo chemoradiotherapy, after which clinical complete responders would be followed nonoperatively and those with persistent residual disease would undergo surgery. 


  • In a study of 14 patients with early-stage rectal cancer, conducted at Memorial Sloan Kettering Cancer Center, preoperative treatment with single-agent dostarlimab-gxly (an anti–PD-1 agent) led to clinical complete responses in 100%.
  • Median follow-up is 6.8 months, but some patients have been followed for more than 20 months.
  • No patient has yet required additional treatment.
  • If the results can be upheld in larger series, immunotherapy in the neoadjuvant setting may spare many patients with rectal cancer the morbidities associated with current approaches.

The primary objectives were overall response rate to PD-1 blockade with or without chemoradiation and pathologic complete response or clinical complete response rate at 12 months after PD-1 blockade with or without chemoradiation. Only the first primary endpoint is able to be evaluated at this time. 

Overall response was determined by rectal magnetic resonance imaging (MRI) and endoscopic exam; patients were determined to have stable disease, partial response, near complete response, or complete response. Clinical complete response was indicated by an endoscopic visual exam showing disappearance of the primary along with a normal digital rectal exam; the formal criteria for rectal MRI response also had to be met.

“In dMMR rectal cancer, PD-1 blockade may be able to either replace chemotherapy; replace chemotherapy and radiation therapy; or replace chemotherapy, radiation therapy, and surgery,” Dr. Cercek said. The early results of her study suggest the third possibility could become a reality.

DISCLOSURE: Dr. Cercek has served as a consultant or advisor to Bayer, GlaxoSmithKline, Incyte, Janssen, Merck, Seattle Genetics and has received research funding from GlaxoSmithKline, Seattle Genetics, and Inspirna.


1. Cercek A, Lumish MA, Sinopoli JC, et al: Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer. 2022 ASCO Annual Meeting. Abstract LBA5. Presented June 5, 2022.

2. Cercek A, Lumish M, Sinopoli J, et al: PD-1 blockade in mismatch repair–deficient, locally advanced rectal cancer. N Engl J Med. June 5, 2022 (early release online).


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