FDA Grants Priority Review to Dostarlimab for dMMR/MSI-H Rectal Cancer

The FDA has granted priority review to a supplemental biologics license application (sBLA) for dostarlimab (Jemperli) for patients with previously untreated stage II and III mismatch repair deficient (dMMR)/microsatellite instability–high (MSI-H) locally advanced rectal cancer.¹

The sBLA is based on results from the phase 2 AZUR-1 trial (NCT05723562), in which dostarlimab achieved the primary end point by showing a meaningful and sustained clinical complete response (cCR) rate at 12 months in patients with stage II/III dMMR/MSI-H locally advanced rectal cancer.² The PDUFA action date for the sBLA is February 2027; however, the decision could come sooner because the application is eligible for expedited review under the National Priority Voucher program.¹

There were no new safety signals with dostarlimab in AZUR-1. Specific efficacy and safety data from the interim analysis will be shared at a future scientific congress, according to GSK, the developer of dostarlimab.²

About AZUR-1

AZUR-1 is a global, open-label, single-arm, registrational trial evaluating dostarlimab monotherapy in patients with stage II/III dMMR/MSI-H locally advanced rectal cancer.²A total of 154 participants received 9 cycles of dostarlimab over 6 months, administered as a 500-mg intravenous infusion every 3 weeks. The trial was designed to assess sustained cCR at 12 months as its primary objective, with the goal of determining whether dostarlimab monotherapy could enable patients to avoid chemotherapy, radiation, and surgery.²

Prior Study Results With Dostarlimab in Rectal Cancer

The AZUR-1 interim results build on a body of earlier evidence established through collaboration with Memorial Sloan Kettering Cancer Center (MSK) in New York, New York.² In findings from a prior phase 2 study (NCT04165772) conducted by MSK, which established the hypothesis for the AZUR-1 registrational trial, dostarlimab monotherapy produced a clinical complete response (cCR) in all 14 of the first 14 evaluable patients at the time of the initial data presentation, simultaneously reported at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the New England Journal of Medicine.³

At that time, no patients had required chemotherapy, radiation, or surgery, and no disease recurrence had been observed. Updated data from the phase 2 study presented at the 2024 ASCO Annual Meeting showed that the 100% cCR rate was maintained across all 42 patients who completed treatment at a median follow-up of 17.9 months (range, 0.3-50.5), with 24 patients achieving sustained cCR for at least 12 months at a median follow-up of 26.3 months (range, 12.4-50.5).⁴

At the time of the 2024 ASCO update, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health, commented on the significance of the results in an interview with Targeted Oncology:

“It is truly remarkable, a 100% clinical complete response rate. What we now have with time is that 20 of those patients have what they are calling a sustained clinical response of longer than a year. So this is amazing. This is the new era of not just neoadjuvant, but definitive management in rectal cancer. It does not require chemotherapy, does not require radiation, does not require surgery, which is absolutely amazing.”

Regulatory Milestones

Dostarlimab has received both breakthrough therapy designation and fast track designation from the FDA in dMMR/MSI-H rectal cancer.

The FDA granted dostarlimab accelerated approval in August 2021 for adult patients with dMMR recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options, a tumor-agnostic indication that technically encompasses dMMR rectal cancer in the previously treated setting.⁵

REFERENCES

1. Jemperli (dostarlimab) accepted for priority review by the US FDA for dMMR/MSI-H locally advanced rectal cancer. GSK. Published August 24, 2026. Accessed August 24, 2026. https://tinyurl.com/bdd7p2z9

2. Jemperli (dostarlimab) achieves sustained clinical complete responses in dMMR/MSI-H locally advanced rectal cancer. News release. GSK. July 13, 2026. Accessed July 13, 2026. https://tinyurl.com/4vk4e95e

3. 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

4. Cercek A, Lumish M, Sinopoli J, et al. Updated results from a phase 2 trial of dostarlimab monotherapy in patients with dMMR locally advanced rectal cancer. Presented at: 2024 ASCO Annual Meeting; May 31-June 4, 2024; Chicago, IL. Abstract LBA3504.

5. FDA grants accelerated approval to dostarlimab-gxly for dMMR advanced solid tumors. FDA. Updated July 18, 2023. Accessed July 13, 2026. https://tinyurl.com/4d4afn4n