FDA Clears Dostarlimab for a Rare Subtype of Rectal Cancer, Sparing Some Patients Surgery

The FDA on October 19 granted accelerated approval to dostarlimab (Jemperli, GSK) for adults with stage II or III locally advanced rectal cancer carrying a specific molecular marker, opening what could be a surgery-free path for a subset of patients who previously had few options beyond chemoradiation and the operating room.

The approval is narrow by design. <cite index="19-4,19-5">The drug is now approved for adults with stage II or III locally advanced rectal cancer that is microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR), a molecular profile that accounts for roughly 5 to 10 percent of rectal tumors.</cite> Patients have to be identified through an FDA-authorized companion test before they're eligible.

The agency based its decision on AZUR-1, a multicenter, single-arm, open-label phase 2 trial. <cite index="20-2">Efficacy was evaluated in 154 patients with previously untreated, histologically confirmed MSI-H/dMMR stage II or III locally advanced rectal cancer.</cite> That's a single-arm design, which means there's no concurrent control group, and the FDA used response rate rather than survival as its primary endpoint, consistent with the accelerated pathway.

<cite index="21-3">Patients received dostarlimab 500 mg via IV every three weeks for nine cycles unless they experienced unacceptable toxicity or disease progression.</cite> <cite index="22-4">Patients who achieved a clinical complete response at either of the first two post-treatment assessments entered a non-operative management period, during which they were closely monitored for recurrence through regular multi-modal assessments conducted every four months for the first two years and every six months thereafter.</cite>

The headline number the FDA used as its primary endpoint was the sustained clinical complete response rate at 12 months. <cite index="22-5,22-6">In 116 patients evaluable by independent central review, the 12-month clinical complete response rate was 47 percent. An additional 38 patients, or 33 percent, achieved a clinical complete response with less than 12 months of follow-up at data cutoff, and 44 patients, or 38 percent, had near-complete response.</cite>

For patients who want the full picture, the disease-progression data are worth noting. <cite index="20-3">With a median follow-up of 26.3 months, none of the patients with sustained clinical complete response, clinical complete response, or near-complete response experienced disease progression.</cite> And among those who did go to surgery: <cite index="22-8">of the 15 patients who underwent surgery after dostarlimab alone, based on imaging findings suggesting incomplete response, pathological complete response was reported in 12 patients.</cite>

<cite index="23-8">Of 154 patients treated, 71 percent received dostarlimab alone, required no additional treatment, and had no disease progression.</cite> GSK has framed this as evidence that eligible patients may avoid chemoradiation and surgery altogether. That framing is worth examining carefully: this is a single-arm trial in a selected population, and avoiding surgery as an endpoint wasn't pre-specified the way a randomized design would allow.

<cite index="19-11,19-12">The approval was made under the FDA's National Priority Review Voucher pilot program. Continued approval for the indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, GSK noted.</cite> That confirmatory trial requirement matters. Accelerated approvals granted on response-rate surrogates have, in some past cases, not held up when longer-term survival data arrived.

For the roughly one in ten rectal cancer patients whose tumors carry this MSI-H or dMMR profile, the approval does represent a real change in what a conversation with a colorectal surgeon or medical oncologist will look like. The question clinicians will be pressing going forward is whether that 47 percent 12-month complete response rate translates into durable disease-free survival, and whether watchful waiting in the non-operative management group remains safe over five or ten years. The AZUR-1 follow-up data, as reported in the FDA filing reviewed by Medscape and the ASCO Post, don't yet answer that.

Sources cited:
- FDA.gov (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-locally-advanced-rectal-cancer)
- Medscape (https://www.medscape.com/viewarticle/fda-approves-dostarlimab-rectal-cancer-2026a10013c7)
- The ASCO Post (https://ascopost.com/news/october-2026/fda-approves-dostarlimab-for-msi-hdmmr-locally-advanced-rectal-cancer/)
- Oncology Nursing News (https://www.oncnursingnews.com/view/fda-grants-accelerated-approval-to-dostarlimab-in-dmmr-rectal-cancer)
- Oncology News Central (https://www.oncologynewscentral.com/drugs/info/fda-approves-dostarlimab-in-untreated-locally-advanced-rectal-cancer)