FDA Accelerates Dostarlimab Approval for MSI-H/dMMR Rectal Cancer

Key Takeaways

• The FDA granted accelerated approval for adults with MSI-H or dMMR stage II/III locally advanced rectal cancer identified by an FDA-authorized solid-tumor test.
• Independent review found sustained clinical complete responses after dostarlimab, without establishing pathological clearance in patients who did not undergo surgery.
• Some AZUR-1 participants received dostarlimab alone without subsequent treatment or disease progression, although others followed different treatment pathways.
• Investigator assessment yielded a higher sustained clinical complete response estimate in a distinct evaluable group, not a head-to-head treatment comparison.

A monitored clinical complete response in microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) rectal cancer does not establish pathological tumor clearance. For adults with locally advanced disease, a nonoperative pathway depends on serial assessments that can identify response, recurrence or progression. Subsequent surgery or other treatment remains relevant when a complete clinical response is not observed. Dostarlimab-treated participants underwent serial assessments to track response and subsequent treatment.

On October 19, 2026, the Food and Drug Administration (FDA) granted accelerated approval of dostarlimab (Jemperli) for adults with MSI-H or dMMR stage II/III locally advanced rectal cancer, as determined by an FDA-authorized test for solid tumors. AZUR-1 (NCT05723562), a multicenter, single-arm, open-label trial, enrolled 154 previously untreated patients with histologically confirmed disease. Its independent central review (ICR) population included 116 evaluable patients; a separate investigator-assessed population included 144. Participants received intravenous dostarlimab. Endoscopy, rectal magnetic resonance imaging (MRI), and chest, abdominal and pelvic computed tomography (CT) informed initial and post-treatment assessments. Complete responders underwent repeated multimodal monitoring without immediate surgery. The primary endpoint was clinical complete response (cCR) sustained for 12 months (cCR12) by ICR; investigator-assessed cCR12 and objective response rate (ORR) were additional measures. The FDA also reviewed a distinct investigator-led, multicenter, single-arm, open-label trial (NCT04165772).

In the ICR-evaluable AZUR-1 group, cCR12 was 47% (95% CI, 27%–56%). This endpoint reflected a sustained clinical response under assessment, not pathological confirmation of tumor clearance.

Among treated AZUR-1 participants, 110 (71%) received dostarlimab alone without additional treatment or disease progression. Other participants underwent surgery, received systemic therapy or radiation, experienced progression without further treatment, or withdrew or were lost to follow-up. During a median follow-up of 26.3 months, no progression was observed among patients with cCR12, cCR or near complete response; that observation did not extend to every treated participant.

Investigator-assessed cCR12 was 68% (95% CI, 60%–76%) in its distinct evaluable group. The investigator and ICR estimates came from different assessments and populations, not competing treatments. Among patients operated on after dostarlimab alone because imaging suggested incomplete response, 12 of 15 had a pathological complete response. The separately reviewed investigator-led trial also reported sustained clinical complete and objective responses; its participants were not part of AZUR-1.

Clinical assessment during nonoperative monitoring cannot establish pathological clearance in patients who do not undergo surgery or demonstrate long-term cure. Neither trial included a randomized standard-treatment comparator, and some ICR-assessed complete responders had less than a year of observation. The prescribing information warns of immune-mediated adverse reactions, infusion reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity. Participants without cCR, or with recurrence or progression, were evaluated for standard-of-care management at investigator discretion.

For adults with MSI-H or dMMR stage II/III locally advanced rectal cancer, the accelerated approval reflects clinically assessed responses and observed nonoperative pathways, while long-term outcomes and comparative benefit remain unresolved.

Clinician Questions

When does the 12-month clinical complete response period begin for dostarlimab-treated MSI-H/dMMR rectal cancer?

In AZUR-1's previously untreated MSI-H/dMMR stage II/III locally advanced rectal cancer population, ICR-assessed cCR12 began at the first disease assessment after the final dostarlimab dose at which cCR was observed, not at enrollment or treatment initiation.

What dostarlimab dose and schedule were used for MSI-H/dMMR locally advanced rectal cancer?

Adults with MSI-H/dMMR stage II/III locally advanced rectal cancer in AZUR-1 received dostarlimab 500 mg intravenously every three weeks for up to nine cycles, stopping earlier for progression or unacceptable toxicity. The FDA-recommended regimen uses the same schedule.

Did patients in the separately reviewed dostarlimab trial for MSI-H/dMMR rectal cancer receive chemoradiation or rectal surgery?

In the distinct investigator-led, single-arm trial, none of the 50 previously untreated patients with MSI-H/dMMR stage II/III locally advanced rectal cancer received chemoradiation or rectal cancer surgery as treatment for locally advanced rectal cancer. That finding does not describe every AZUR-1 participant.