Dostarlimab for dMMR/MSI-H Locally Advanced Rectal Cancer: FDA Accelerated Approval and AZUR-1

　　1.Approval Snapshot

　　Dostarlimab-gxly(Jemperli),a PD-1 blocker from GSK,received FDA accelerated approval on 19 Oct 2026 as monotherapy for adults with previously untreated stage II or III locally advanced rectal cancer confirmed dMMR or MSI-H by an FDA-authorized test.

　　Goal:tumor control allowing some patients to defer or avoid standard neoadjuvant chemoradiation and radical surgery.

　　Accelerated approval still requires confirmatory long-term data.

　　2.Why dMMR/MSI-H Only

　　dMMR/MSI-H tumors carry mismatch-repair deficiency and high mutational burden,making them visible to T-cell immunity and sensitive to PD-1 blockade.

　　pMMR/MSS rectal cancer is outside this indication.Testing must be done before treatment;multidisciplinary evaluation is required.

　　3.AZUR-1 Data

　　AZUR-1(NCT05723562):open-label single-arm phase II,n=154 treatment-naive dMMR/MSI-H locally advanced rectal cancer.

　　Regimen:IV dostarlimab every 3 weeks,max 9 cycles(~6 months).

　　Primary endpoint:sustained clinical complete response at 12 months(cCR12).

　　Investigator-assessed:68%(98/144);

　　Independent central review:47%(54/116);

　　Exploratory:76%(110/144)no evidence of cancer at≥1 year,some without surgery;

　　Median follow-up>2 years,no progressions reported among responders.

　　Earlier MSK small-cohort data showed very high cCR but are background only.

　　4.Clinical Meaning and Limits

　　Standard locally advanced rectal cancer path is neoadjuvant chemoradiation+surgery,with bowel/urinary/sexual/fertility and stoma burden.dMMR/MSI-H subset is small but highly immunotherapy-sensitive,enabling organ-preservation or watch-and-wait.

　　Cautions:

　　not all rectal cancer;

　　not guaranteed avoidance of surgery;

　　cCR still needs endoscopy,MRI,digital exam,biopsy;

　　recurrence/progression returns to chemoradiation/surgery;

　　accelerated approval may change with maturity data.

　　5.Safety

　　Immune-mediated adverse events:

　　colitis:diarrhea,abdominal pain,bleeding;

　　hepatitis:transaminitis,jaundice;

　　pneumonitis:cough,dyspnea;

　　endocrine:thyroid disease,hypophysitis,adrenal insufficiency,hyperglycemia;

　　rash,pruritus;

　　infusion reactions,fatigue.

　　Common:fatigue,rash,diarrhea,itch.

　　Grade≥3:hold or discontinue per immune-management guidelines;avoid in pregnancy/lactation.

　　6.Follow-up Pathway

　　Confirm dMMR/MSI-H;

　　MDT discussion;

　　Dosing every 3 weeks×9;

　　Endoscopy/MRI/CBC/LFT/thyroid monitoring;

　　12-month cCR assessment;

　　Non-surgical follow-up if cCR;chemoradiation/surgery if not.