FDA Grants Accelerated Approval to Dostarlimab in dMMR Rectal Cancer

The FDA granted accelerated approval to dostarlimab (Jemperli) on October 19, 2026, for adults with stage II/III locally advanced rectal cancer (LARC) that is microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR), as determined by an FDA-authorized test for solid tumors.

In the single-arm phase 2 AZUR-1 trial (NCT05723562), 71% of 154 treated patients received dostarlimab alone with no additional treatment and no disease progression, and the sustained 12-month clinical complete response (cCR12) rate was 47% per independent central review (ICR).

For oncology nurses, the indication introduces a nonoperative management pathway in which responding patients forgo chemotherapy, radiation, and surgery but return for multimodal surveillance every few months for years.

How was the AZUR-1 trial designed?

AZUR-1 is a multicenter, single-arm, open-label trial that enrolled 154 patients with previously untreated, histologically confirmed MSI-H/dMMR stage II/III LARC. Patients received dostarlimab 500 mg intravenously every 3 weeks for 9 cycles, or about 6 months of treatment, unless unacceptable toxicity or disease progression occurred.

Tumor response was assessed with endoscopy, rectal MRI, and CT of the chest, abdomen, and pelvis at week 6, week 12, and approximately 3 weeks after treatment completion. Patients with a clinical complete response (cCR) at either of the first 2 post-treatment assessments entered a nonoperative management period, with multimodal assessments every 4 months for the first 2 years and every 6 months thereafter. Patients without a cCR, or whose disease recurred or progressed, were evaluated for standard-of-care management at investigator discretion.

The primary end point was cCR12 per ICR, measured from the first disease assessment after the last dose of dostarlimab at which cCR was observed. Additional end points included investigator-assessed cCR12 and objective response rate (ORR) per ICR and per investigator.

What were the efficacy results in AZUR-1?

Of the 154 treated patients:

• 110 (71%) received dostarlimab alone, had no additional treatment, and did not experience disease progression
• 26 (17%) underwent surgery, with or without additional systemic therapy or radiation
• 13 (8%) received additional systemic therapy or radiation
• 1 (0.6%) had progressive disease without further treatment
• 4 (2.5%) withdrew or were lost to follow-up

Among 116 ICR-evaluable patients, the cCR12 rate was 47% (95% CI, 27%-56%) and the ORR was 79% (95% CI, 71%-85%). At data cutoff, an additional 38 patients (33%) had achieved cCR by ICR but had less than 12 months of follow-up, and 44 (38%) had a near complete response (nCR). With a median follow-up of 26.3 months, no patient with cCR12, cCR, or nCR had experienced disease progression.

Among 144 investigator-evaluable patients, the cCR12 rate was 68% (95% CI, 60%-76%) and the ORR was 82% (95% CI, 75%-88%). In an exploratory analysis reported by GSK, 76% of evaluable patients had no evidence of cancer 1 year or more after treatment.

Of the 15 patients who underwent surgery after dostarlimab alone because imaging suggested an incomplete response, 12 had a pathologic complete response.

What supporting data did the FDA review?

The FDA also reviewed an investigator-led, multicenter, single-arm, open-label trial (NCT04165772) of the same regimen in 50 patients with previously untreated MSI-H/dMMR stage II/III LARC. The cCR12 rate was 93% (95% CI, 82%-99%) and the ORR was 100% (95% CI, 93%-100%). No patients received chemoradiation or rectal cancer surgery as part of their LARC treatment. Among 27 patients followed for at least 3 years, 1 had a local recurrence treated with lymphadenectomy, 1 withdrew, and 1 died of a cause unrelated to the disease under study.

That trial, led at Memorial Sloan Kettering Cancer Center (MSK), first reported a cCR in all 12 patients who had completed treatment in 2022, and later reported a cCR in all 49 patients who completed treatment in its rectal cancer cohort. Oncology Nursing News covered the initial readout at the 2022 ASCO Annual Meeting, where lead investigator Andrea Cercek, MD, section head of colorectal cancer at MSK, said, "No patients have required chemotherapy, radiation, or surgery [and] there has been no disease recurrence observed during the follow-up period."

What safety findings should nurses know about?

According to GSK, serious adverse reactions occurred in 20% of patients who received dostarlimab in AZUR-1. The most common adverse reactions were fatigue (32%), rash (22%), diarrhea (18%), and pruritus (17%), and 3% of patients permanently discontinued treatment because of adverse reactions.

The prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity. The recommended dose is 500 mg every 3 weeks for up to 9 cycles, until disease progression or unacceptable toxicity.

Why does this approval matter, and what are its limitations?

Approximately 5% to 10% of rectal cancers are dMMR/MSI-H. Standard care for LARC typically includes chemotherapy, radiation, and surgery, which can lead to lifelong colostomy use, physiological dysfunction, and infertility.

The FDA approved the application 4 months ahead of its goal date. The application received priority review and was part of the FDA Commissioner's National Priority Voucher pilot program, and dostarlimab had received breakthrough therapy designation. The review used the Real-Time Oncology Review program and was conducted under Project Orbis with Health Canada, Israel's Ministry of Health, Swissmedic, and the United Kingdom's Medicines and Healthcare products Regulatory Agency, whose reviews are ongoing.

Both trials were single arm, with no comparator group. The ICR-assessed and investigator-assessed cCR12 rates differed (47% vs 68%), and one-third of ICR-evaluable patients with a cCR had less than 12 months of follow-up at data cutoff. Under the accelerated approval pathway, continued approval may be contingent on verification of clinical benefit. AZUR-1 is sponsored by GSK, and full interim data are scheduled for presentation at the European Society for Medical Oncology Congress 2026.

What are the key takeaways for oncology nurses?

• Confirm biomarker status first. The indication requires MSI-H/dMMR status determined by an FDA-authorized test, so results should be documented before treatment planning.
• Prepare patients for long-term surveillance. In AZUR-1, patients in nonoperative management had endoscopy, rectal MRI, and imaging every 4 months for 2 years, then every 6 months. Scheduling, navigation, and travel support can help patients stay on that calendar.
• Monitor for immune-mediated adverse reactions. Fatigue, rash, diarrhea, and pruritus were the most common adverse reactions; new or worsening diarrhea warrants prompt assessment rather than being attributed to the rectal tumor.
• Observe infusions. Infusion-related reactions are listed among the warnings and precautions.
• Counsel on reproductive risk. The prescribing information includes embryo-fetal toxicity, so discussions about pregnancy prevention belong in pretreatment education.
• Set realistic expectations. In AZUR-1, 17% of patients underwent surgery, and 8% received additional systemic therapy or radiation, so shared decision-making should address what happens if a complete response is not reached.
• Report adverse events. Serious adverse events suspected to be associated with dostarlimab can be reported to FDA MedWatch or 1-800-FDA-1088.

References

1. FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer. FDA. October 19, 2026. Accessed October 19, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-locally-advanced-rectal-cancer
2. GSK's Jemperli wins FDA approval for rectal cancer treatment. Investing.com. October 19, 2026. Accessed October 19, 2026. https://uk.investing.com/news/stock-market-news/gsks-jemperli-wins-fda-approval-for-rectal-cancer-treatment-93CH-4918141
3. Jemperli (dostarlimab) achieves sustained clinical complete responses in dMMR/MSI-H locally advanced rectal cancer. News release. GSK. July 13, 2026. Accessed October 19, 2026. https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-achieves-sustained-clinical-complete-responses-in-dmmrmsi-h-locally-advanced-rectal-cancer/
4. 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(25):2363-2376. doi:10.1056/NEJMoa2201445
5. Cercek A, Foote MB, Rousseau B, et al. Nonoperative management of mismatch repair-deficient tumors. N Engl J Med. 2025;392(23):2297-2308. doi:10.1056/NEJMoa2404512
6. Lovely B. All patients with dMMR rectal cancer experience clinical complete response with dostarlimab in phase 2 trial. Oncology Nursing News. June 8, 2022. Accessed October 19, 2026. https://www.oncnursingnews.com/view/all-patients-with-dmmr-rectal-cancer-experience-clinical-complete-response-with-dostarlimab-in-phase-2-trial
7. A study of dostarlimab in untreated dMMR/MSI-H locally advanced rectal cancer (AZUR-1). ClinicalTrials.gov identifier: NCT05723562. Updated May 26, 2026. Accessed October 19, 2026. https://clinicaltrials.gov/study/NCT05723562