The FDA set a target action date of February 2027 for the dostarlimab-gxly sBLA in dMMR/MSI-H locally advanced rectal cancer.
The FDA has granted priority review to a supplemental biologics license application (sBLA) to dostarlimab-gxly (Jemperli) for the treatment of patients with previously untreated, stage II and III mismatch repair–deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced rectal cancer.1
The agency assigned a target action date of February 2027 under the Prescription Drug User Fee Act, and the application is also eligible for expedited review through the National Priority Voucher program.
The sBLA is supported by data from the phase 2 AZUR-1 trial (NCT05723562), evaluating dostarlimab monotherapy in patients with previously untreated stage II/III dMMR/MSI-H locally advanced rectal cancer (n = 154).1,2 The trial met its primary end point of showing sustained clinical complete response at 12 months (cCR12), full efficacy data are scheduled for presentation later in 2026.
“The AZUR-1 results support the potential for dostarlimab to transform treatment for dMMR/MSI-H locally advanced rectal cancer,” Hesham Abdullah, senior vice president, global head oncology, R&D at GSK, stated previously in a news release about the trial.3 “For many patients today, rectal cancer treatment comes with the tolerability burden and lasting impacts from chemotherapy, radiation and surgery. These data demonstrate that some patients may be able to avoid those interventions while remaining free of detectable signs of cancer.”
The multicenter, open label study enrolled patients who were at least 18 years of age with radiologically and endoscopically evaluable stage II to III disease that could be recognized as dMMR or MSI-H by local or central assessment, and an ECOG performance status of 1 or less .2,4
If patients had distant metastatic disease, received prior radiation therapy, systemic therapy, or surgery for rectal cancer, a history of interstitial lung disease, or had known additional malignancies that progressed or required active treatment within the past 2 years, they were not included in the trial.
Participants received dostarlimab monotherapy at 500 mg intravenously every 3 weeks for 9 cycles over 6 months.1,2
The trial's primary end point was cCR12 whereas key secondary end points were 24- and 36-month cCR rates and 3-year event free survival.
The safety and tolerability profile of dostarlimab in the trial was generally consistent with safety profile previously observed across solid tumors.1
Previous data from a phase 2 study (NCT04165772) showed that patients with dMMR locally advanced rectal cancer who received dostarlimab monotherapy (n = 42) all achieved a cCR in addition to, at a median follow-up of 26.3 months (range, 12.4-50.5), 24 patients experiencing a cCR12. Moreover, patients in this trial demonstrated a median time to cCR of 6.22 months (95% CI, 6.18-6.45).5
Safety data from the previously reported trial reported common adverse effects experienced by patients as rash/dermatitis (21%), pruritus (13%), fatigue (11%), and hypothyroidism (11%).
Dostarlimab was previously granted fast track and
