FDA grants GSK's Jemperli accelerated approval in dMMR locally advanced rectal cancer

The US Food and Drug Administration granted accelerated approval on 19 October 2026 to GSK's Jemperli (dostarlimab-gxly) as a single agent for adults with previously untreated stage II or III locally advanced rectal cancer whose tumours are mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) ¹. GSK says it is the first and only immunotherapy approved in the US for this group ².

The approval matters because the standard route for these patients is chemotherapy and radiation before surgery, which the FDA says can affect bowel, urinary and sexual function and fertility, and surgery can end in a permanent colostomy for some ¹. Jemperli is a PD-1 blocking antibody, and dMMR or MSI-H tumours accumulate DNA errors that make them more visible to the immune system ¹.

What the trial found

The FDA based its decision on interim results from AZUR-1, a phase 2, open-label, single-arm study of Jemperli alone in 154 patients, who received up to nine doses every 3 weeks over 6 months ¹². After a median follow-up of more than 2 years, the FDA reports that almost three-fourths of patients had not needed surgery, radiotherapy or chemotherapy ¹.

GSK gives the detail. On investigator assessment, 68% of evaluable patients (98 of 144) reached a sustained clinical complete response at 12 months, the trial's main measure ². In an exploratory analysis, 76% (110 of 144) had no evidence of cancer one year or more after treatment, a figure that adds 12 patients whose complete response was confirmed on tissue after surgery ². The formal primary endpoint, assessed by independent central review, is still maturing: so far 47% (54 of 116) have reached it, and another 38 participants who already have a clinical complete response have not yet reached 12 months of follow-up ². GSK says no responder has relapsed to date ².

The FDA also points to an earlier Memorial Sloan Kettering study of 50 patients, in which none had detectable cancer after treatment and 93% stayed cancer-free for at least 12 months. Of 27 followed for at least 3 years, one relapsed ¹. Serious adverse reactions occurred in 20% of AZUR-1 patients and 3% stopped treatment because of them; the most common were fatigue (32%), rash (22%), diarrhoea (18%) and itching (17%) ².

What it means for the market

For oncology teams the approval turns a biomarker into the gate for a treatment that may replace three standard interventions, which puts weight on testing at diagnosis. Eligibility requires an FDA-authorised test, and the patient advocate GSK quotes says biomarker testing at diagnosis "will be essential" to finding who qualifies ¹². The population is narrow. The FDA cites published estimates that approximately 3% of locally advanced rectal cancers are dMMR or MSI-H, while GSK puts the biomarker at around 5-10% of rectal cancers ¹².

For regulatory teams the speed is the point. The FDA says the review finished nearly 4 months ahead of schedule and is the 11th approval under the Commissioner's National Priority Voucher pilot programme, on top of priority review and breakthrough therapy designation ¹. The application is also under Project Orbis, which lets other health authorities review it at the same time, and GSK says reviews in participating countries are ongoing ².

The limits are stated plainly. This is an accelerated approval on interim, single-arm data, so GSK must keep following patients to show the responses give lasting benefit, and the FDA says longer follow-up is needed to understand how long responses last and how often the cancer returns ¹. The label itself says the long-term risk of relapse is unknown ². GSK will present the full AZUR-1 interim analysis at the ESMO Congress in October 2026 ².