Approved treatment — U.S. FDA accelerated approval (2026-10-19), dMMR/MSI-H stage II–III locally advanced rectal cancer Canada, UK, Switzerland, Israel — reviews ongoing
There is important news for rectal cancer immunotherapy. On October 19, 2026, the U.S. FDA granted accelerated approval to the immunotherapy drug dostarlimab (brand name Jemperli) as first treatment for adults with stage II–III locally advanced rectal cancer that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H). In the AZUR-1 trial, 71% of treated patients received dostarlimab alone, needed no further treatment and had no disease progression, and many kept their rectum without chemoradiation or surgery.
What was newly approved: immunotherapy alone instead of the usual pre-surgery treatment
For many years, standard care for locally advanced rectal cancer has been chemoradiation and chemotherapy followed by surgery to remove the rectum. It works, but it can leave people with a permanent stoma (colostomy), changes in bowel, bladder and sexual function, and in some cases reduced fertility from radiation.
This is the first immunotherapy approval that can change that sequence. Dostarlimab blocks PD-1, a "brake" on immune cells, helping the body's immune system attack cancer cells. It is given as a 500 mg intravenous infusion every 3 weeks for up to nine cycles (about 6 months). If endoscopy, rectal MRI and CT show no visible cancer after treatment (clinical complete response, cCR), patients move to non-operative management ("watch and wait") with regular check-ups instead of surgery.
Accelerated approval lets the FDA approve a drug based on strong early results while longer follow-up continues to confirm the benefit. The FDA gave this application priority review and approved it four months ahead of its goal date.
Who it is for: dMMR/MSI-H stage II–III rectal cancer
The approval covers adults who meet all of the following:
- Rectal cancer confirmed as dMMR or MSI-H by an FDA-authorized test
- Stage II or III locally advanced disease that has not spread to distant organs
- No previous chemotherapy, radiation or surgery for the cancer (as in AZUR-1)
dMMR/MSI-H tumors have a weakened ability to repair DNA copying errors. A U.S. patient organization describes them as less than 10% of rectal cancers. Many are linked to Lynch syndrome, an inherited colorectal cancer condition, so genetic counseling for the patient and family is often recommended. The status can be checked on the biopsy tissue with immunohistochemistry (MMR proteins) or an MSI test, so if you have been diagnosed with rectal cancer, ask whether this test has been done.
AZUR-1 and U.S. study results: most patients managed without surgery
The approval is based on AZUR-1 (NCT05723562), an international, multicenter, single-arm phase 2 trial. Of 154 treated patients, 116 could be assessed by independent central review. Median follow-up was 26.3 months.
| Measure (AZUR-1) | Result |
|---|---|
| Complete response sustained ≥12 months (cCR12, central review) | 47% |
| Complete response with <12 months of follow-up (central review) | 33% |
| Near-complete response (central review) | 38% |
| Objective response rate (central review) | 79% |
| cCR12 / response rate (investigator, 144 patients) | 68% / 82% |
| Dostarlimab alone, no further treatment, no progression | 110 (71%) |
Source: U.S. FDA approval notice (2026-10-19). Single-arm trial; results are reported for dostarlimab without a comparison group.
No patient with a complete or near-complete response had disease progression. Of the 26 patients (17%) who had surgery, 15 did so because imaging suggested an incomplete response, and 12 of these had no cancer cells left in the removed tissue (pathological complete response).
The FDA also reviewed a study led by Memorial Sloan Kettering Cancer Center (NCT04165772). In its 50 rectal cancer patients, the 12-month sustained complete response rate was 93% and the response rate was 100%, and no one needed chemoradiation or rectal surgery as part of treatment. Among 27 patients followed for at least 3 years, one had a local recurrence, which was treated by lymph node removal. In 2025 the same team reported in NEJM that all 49 rectal cancer patients reached complete response, with a 2-year recurrence-free survival of 96%.
Side effects and management: spot immune-related symptoms early
In the early study published in NEJM in 2022 (safety analysis of 16 patients), common side effects were rash (31%), itchy skin (25%), fatigue (25%) and nausea (19%), and no grade 3 or higher adverse events were reported. PD-1 inhibitors can still cause immune-related reactions in which the immune system affects healthy organs (thyroid changes, pneumonitis, colitis, hepatitis and others). The FDA label includes warnings for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic stem cell transplantation and embryo-fetal toxicity. Regular blood tests (thyroid and liver function) and telling your team promptly about diarrhea, cough or severe tiredness allow most of these to be managed, often with steroids.
After moving to non-operative management, regular endoscopy and MRI are essential. If regrowth is found, standard treatment such as surgery can still follow, so keeping the check-up schedule is central to this approach.
Where it is available: approved in the U.S., under review in four more countries
- United States: FDA accelerated approval on October 19, 2026 (approved treatment).
- Canada, UK, Switzerland, Israel: reviews are ongoing through Project Orbis, an international program that reviews cancer drugs alongside the FDA.
- Japan and other countries: as of the check date (2026-10-21), no approval for this rectal cancer use has been announced yet. Watch for announcements from regulators and the manufacturer (GSK).
A follow-up trial (NCT07740720) is registered to study whether the treatment period can be shortened. If you are considering treatment abroad, first check the approved use and costs in that country. Guidance on reading information from Japanese medical institutions is available in Other Japan medical information.
What to check and questions for your doctor
- Has my tumor tissue been tested for MMR proteins or MSI? Is it dMMR/MSI-H?
- For my stage (II or III) and tumor location, can dostarlimab alone be considered first?
- If I reach complete response, how often will I need endoscopy and MRI?
- If the response is not enough, when and to what treatment would we switch?
- Do I need genetic testing for Lynch syndrome, and should my family be screened?
Frequently asked questions
Can rectal cancer immunotherapy really let me avoid surgery?
For dMMR/MSI-H rectal cancer, the chance is high. In AZUR-1, 71% received dostarlimab alone with no further treatment and no progression, and in a U.S. study of 50 patients no one needed chemoradiation or surgery. Regular endoscopy and MRI are still essential.
Is dostarlimab used for all rectal cancers?
No. It is for stage II–III locally advanced rectal cancer confirmed as dMMR or MSI-H on tissue testing. This is a subset of rectal cancers, so check your MMR/MSI result first.
How long does dostarlimab treatment take?
It is given by IV infusion every 3 weeks for up to nine doses, about 6 months. Response is checked with endoscopy, rectal MRI and CT during and after treatment.
What are the side effects of dostarlimab?
In the early study, rash, itchy skin, fatigue and nausea were common, and no grade 3 or higher adverse events were reported. Immune-related reactions are managed with regular blood tests and early reporting.
Related: FDA Approves Atezolizumab for Stage III dMMR Colon Cancer · BCG-unresponsive bladder cancer: Anktiva · All articles by cancer type
Sources
- U.S. FDA — FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer (2026-10-19)
fda.gov
Checked: 2026-10-21 - Cercek A, Foote MB, Rousseau B, et al. Nonoperative management of mismatch repair–deficient tumors. N Engl J Med 2025
doi.org/10.1056/NEJMoa2404512
Checked: 2026-10-21 - Cercek A, Lumish M, Sinopoli J, et al. PD-1 blockade in mismatch repair–deficient, locally advanced rectal cancer. N Engl J Med 2022;386:2363-2376
doi.org/10.1056/NEJMoa2201445
Checked: 2026-10-21 - ClinicalTrials.gov — A Study of Dostarlimab in Untreated dMMR/MSI-H Locally Advanced Rectal Cancer (AZUR-1, NCT05723562)
clinicaltrials.gov/study/NCT05723562
Checked: 2026-10-21 - FORCE (Facing Our Risk of Cancer Empowered) — XRAY: Dostarlimab for rectal cancer
facingourrisk.org
Checked: 2026-10-21
Written by the FTH editorial team. Sources checked 2026-10-21 · Medical review: not applicable
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your medical team.
