In trials, most patients given the immunotherapy alone avoided chemotherapy, radiation and surgery, but the FDA wants longer follow-up before calling the benefit lasting.
For decades, the road through locally advanced rectal cancer has run through chemotherapy, radiation and surgery, often with lasting effects on bowel, bladder and sexual function. On October 19, 2026, the US Food and Drug Administration granted accelerated approval to an immunotherapy that may let a small, genetically defined group of patients skip all three [1][2].
The drug is dostarlimab (Jemperli, GSK), an antibody that blocks the PD-1 immune checkpoint. The approval covers adults with stage II or III locally advanced rectal cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), as determined by an FDA-authorized test [1]. Rarely does a cancer approval's headline consist mostly of things patients may not have to do.
Background
Tumors that lack working DNA mismatch repair pile up mutations, which tends to make them more visible to the immune system. The FDA estimates that about 3% of locally advanced rectal cancers fall into this group [2].
The idea of treating these tumors with checkpoint blockade alone drew wide attention after investigators at Memorial Sloan Kettering Cancer Center (MSK) reported early results in the New England Journal of Medicine in 2022 [5]. A larger 2025 NEJM update from the same group reported clinical complete responses in all 49 patients with rectal cancer who completed dostarlimab [6][7].
What the FDA Approved, and on What Evidence
The approval rests mainly on AZUR-1 (NCT05723562), a multicenter, single-arm, open-label trial that enrolled 154 patients with previously untreated MSI-H/dMMR stage II/III disease [1]. GSK describes it as a registrational phase 2 study [3]. Patients received 500 mg of dostarlimab intravenously every three weeks for up to nine cycles [1].
The primary endpoint was a clinical complete response sustained for 12 months (cCR12), judged by independent central review. Among 116 evaluable patients, 47% (54 of 116) reached it; GSK reports a 95% confidence interval of 37% to 56% [3]. The objective response rate by central review was 79% (95% CI, 71% to 85%), and median follow-up was 26.3 months [1]. When investigators made the call instead, the cCR12 rate was 68% among 144 evaluable patients [1].
According to trial data reported by The ASCO Post, 110 patients (71%) were treated with dostarlimab alone with no further treatment or disease progression, while 26 (17%) went on to surgery [4]. The FDA summarized that almost three-fourths of patients had not needed surgery, radiotherapy or chemotherapy after a median follow-up of more than two years [2].
Supporting evidence came from a second, investigator-led single-arm trial (NCT04165772) of 50 patients. Its cCR12 rate was 93% (95% CI, 82% to 99%), the response rate was 100%, and no patient received chemoradiation or rectal cancer surgery as part of their treatment [1]. Of 27 patients followed for at least three years, one had a local recurrence [1].
Angelo de Claro, MD, who directs the FDA's Oncology Center of Excellence, called the approval "a groundbreaking option that avoids surgery, radiation and chemotherapy" [2]. The drug was reviewed under Priority Review, Breakthrough Therapy designation and the Real-Time Oncology Review program, and was approved four months ahead of its goal date [1]. It was the 11th approval under the Commissioner's National Priority Voucher pilot program [2].
Study Design and Limitations
Both trials were single-arm, with no randomized comparison against standard chemoradiation and surgery. Accelerated approval is based on response rates rather than survival, and the FDA said the sponsor must keep following patients to show that responses translate into lasting clinical benefit [2].
The gap between the centrally reviewed cCR12 rate (47%) and the investigator-assessed rate (68%) is notable; the 47% figure is the trial's primary result [1]. The AZUR-1 figures come from the FDA review and GSK. GSK says full interim data will be presented at the European Society for Medical Oncology (ESMO) Congress in October 2026, so a peer-reviewed report is still to come [3].
AZUR-1 is GSK's trial [3]. The 2025 NEJM study was funded by Swim Across America, Stand Up To Cancer, the NIH/National Cancer Institute and GSK, and its lead investigators disclosed financial ties to GSK [7].
On safety, GSK reports serious adverse reactions in 20% of patients and permanent discontinuation due to adverse reactions in 3%. The most common side effects were fatigue (32%), rash (22%), diarrhea (18%) and itching (17%) [3]. The FDA label carries warnings for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic stem cell transplant and embryo-fetal toxicity [1].
Clinical and Patient Implications
For eligible patients, the approval turns mismatch repair or MSI testing at diagnosis into a decision point with large consequences. Avoiding treatment, however, does not mean avoiding follow-up. In AZUR-1, response was assessed with endoscopy, rectal MRI and CT scans, and patients managed without surgery were checked every four months for two years, then every six months [4].
The approval also applies only to the small dMMR/MSI-H subset. Most rectal cancers are mismatch repair proficient, and for those patients standard multimodal treatment remains the norm.
What Comes Next
Attention now turns to the full AZUR-1 presentation at ESMO and to longer follow-up on durability [2][3]. Reviews through the FDA's Project Orbis are under way with Health Canada, Israel's Ministry of Health, Swissmedic and the UK's MHRA [1]. Whether "watch and wait" becomes a durable standard for this group will depend on what the next several years of surveillance show.
This article is for informational purposes only and is not medical advice; readers should consult their clinician about their own care.
References
US Food and Drug Administration. FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer. FDA, Resources for Information: Approved Drugs. October 19, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-locally-advanced-rectal-cancer
US Food and Drug Administration. FDA Approves Immunotherapy That May Allow Certain Patients with Rectal Cancer to Avoid Chemotherapy, Radiation and Surgery. FDA press announcement. October 19, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-immunotherapy-may-allow-certain-patients-rectal-cancer-avoid-chemotherapy-radiation-and
GSK plc. Jemperli (dostarlimab) approved in US as first and only immunotherapy for adults with MSI-H/dMMR locally advanced rectal cancer. GSK press release. October 19, 2026. https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-approved-in-us-as-first-and-only-immunotherapy-for-adults-with-msi-hdmmr-locally-advanced-rectal-cancer/
The ASCO Post Staff. FDA Approves Dostarlimab for MSI-H/dMMR Locally Advanced Rectal Cancer. The ASCO Post. October 19, 2026 (updated October 20, 2026). https://ascopost.com/news/october-2026/fda-approves-dostarlimab-for-msi-hdmmr-locally-advanced-rectal-cancer/
Cercek A, Lumish M, et al. PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022;386:2363-2376. doi:10.1056/NEJMoa2201445. https://www.nejm.org/doi/full/10.1056/NEJMoa2201445
Cercek A, Foote MB, Rousseau B, et al. Nonoperative Management of Mismatch Repair–Deficient Tumors. N Engl J Med. 2025. doi:10.1056/NEJMoa2404512. https://www.nejm.org/doi/full/10.1056/NEJMoa2404512
The ASCO Post Staff. Nonoperative Management of Mismatch Repair–Deficient Tumors. The ASCO Post. April 28, 2025. https://ascopost.com/news/april-2025/nonoperative-management-of-mismatch-repair-deficient-tumors/
