FDA Grants Accelerated Approval to Dostarlimab (Jemperli) for MSI-H/dMMR Rectal Cancer — Immunotherapy-First Organ Preservation Becomes a Labeled Paradigm
October 19, 2026 (approval date; confirmed on FDA's site this cycle). The FDA granted accelerated approval to dostarlimab (Jemperli, GSK) for adults with Stage II/III locally advanced rectal cancer (LARC) that is microsatellite instability-high or mismatch-repair deficient (MSI-H/dMMR) — the approval that codifies the "immunotherapy instead of surgery, radiation, and chemo" paradigm for dMMR rectal cancer.
The pivotal support is AZUR-1 (NCT05723562), a multicenter single-arm trial in 154 previously untreated patients. The FDA's approval page states: "Of 154 treated patients, 110 (71%) were treated with dostarlimab alone, did not receive any additional form of treatment, and did not experience disease progression12" — i.e., roughly seven in ten patients were spared surgery, radiation, and chemotherapy entirely. The primary endpoint, sustained clinical complete response at 12 months (cCR12) per independent central review, was 47% (95% CI: 27%, 56%) with an ORR of 79% per ICR; investigator-assessed cCR12 was 68%. "With a median follow up of 26.3 months, none of the patients with cCR12, cCR, or nCR experienced disease progression."
FDA also reviewed the investigator-led trial that made this story famous (NCT04165772, 50 patients, the Memorial Sloan Kettting-lineage dMMR rectal cohort): "The cCR12 rate was 93% (95% CI: 82%, 99%) and the ORR was 100% (95% CI: 93%, 100%). No patients received chemoradiation and/or rectal cancer surgery as part of the treatment of LARC." Of the 27 patients followed at least 3 years, 1 had a local recurrence (treated with lymphadenectomy), 1 withdrew, and 1 died of causes unrelated to the disease under study.
Process notes from the FDA page: the review ran under Project Orbis (with Health Canada, Israel's IMoH, Swissmedic, and UK's MHRA — partner reviews still ongoing), used Real-Time Oncology Review and the Assessment Aid, and was approved 4 months ahead of the FDA goal date as part of the Commissioner's National Priority Voucher (CNPV) pilot program FDA's Commissioner’s National Priority Voucher (CNPV) Pilot Program Accelerates Landmark Approvals to Under Two Months. Dostarlimab holds breakthrough therapy designation and priority review.
What it means. This is the second landmark dMMR-driven approval in under two weeks — following Tecentriq + chemotherapy for Stage III dMMR colon cancer on Oct 8 FDA Approves Tecentriq (Atezolizumab) + Chemotherapy for Stage III dMMR Colon Cancer — Disease-Free Survival HR 0.50 in ATOMIC — but the more radical practice change: for the dMMR subset of rectal cancer patients, PD-1 blockade alone can replace the entire surgical/radiation/chemo sequence, with non-operative management written into the label3 (cCR patients enter monitored surveillance instead of the operating room). Caveats to carry forward: accelerated approval rests on cCR12 as a surrogate endpoint4, the ICR-assessed cCR12 (47%) is well below the investigator-assessed rate (68%), and the confirmatory picture is still forming — the 38 additional ICR cCR patients had less than 12 months of follow-up at data cutoff.
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An instance of In dMMR cancers, checkpoint blockade is now approved instead of surgery. — Seven in ten dMMR rectal patients were spared surgery, radiation, and chemotherapy entirely on a PD-1 label, codifying immunotherapy-instead-of-surgery. ↩︎
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An instance of No cancer driver remains permanently undruggable under precise molecular targeting. — Precise targeting of the MSI-H/dMMR driver lets a single immunotherapy replace the entire surgery-radiation-chemo sequence once thought unavoidable. ↩︎
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An instance of Every approved drug is on a one-way ratchet toward first-line use. — A checkpoint inhibitor's label now covers previously untreated patients as sole therapy displacing an entire treatment sequence — the ratchet's furthest reach into day-one use. ↩︎
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An instance of Unprecedented surrogate biomarkers are replacing clinical outcomes to secure accelerated drug approvals. — A paradigm-shifting organ-preserving label is granted on a 12-month complete-response surrogate rather than survival endpoints, expediting market access ahead of definitive verification. ↩︎