At ESMO Congress 2026, Andrea Cercek, MD, presented interim results from the first global registrational AZUR-1 phase 2 trial (NCT05723562) that evaluated the benefit of neoadjuvant dostarlimab monotherapy in mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC) (LBA87).
Standard of care (SOC) for LARC includes chemotherapy, radiation, and surgery, all of which cause substantial toxicity, morbidity, and quality of life (QoL) burdens. In dMMR/MSI-H LARC, clinical complete response (cCR) rates post-SOC are approximately 20%-25%.
dMMR/MSI-H tumors are very responsive to PD-1 blockade. Monotherapy with dostarlimab, a PD-1 inhibitor, led to durable cCRs in patients with dMMR/MSI-H LARC in a small single center study, supporting non-operative management that may allow patients to avoid surgery, chemotherapy, and radiation.
AZUR-1 is a single arm trial of 9 cycles (6 months) of 500 mg IV dostarlimab every 3 weeks in 154 previously untreated patients with Stage II or III dMMR/MSI-H LARC with no symptomatic bowel obstruction. Responses are assessed 21 days after the last dose by endoscopy and MRI/CT.
The primary endpoint of cCR12 (cCR for ≥12 months) by independent central review (ICR) was mandated by the regulatory agency because AZUR-1 is a single-arm global registration study with a novel endpoint. The secondary endpoint is cCR12 by investigator review. An exploratory endpoint is cCR12 plus pathologic complete response (pCR) assessed by investigator.
Of 136 patients who completed dostarlimab monotherapy, cCR was 71%. The 26% not in cCR received SOC of investigator choice. Median follow-up was 26.3 months.
cCR12 by investigator was 68%; 10 patients have not yet been followed for 12 months. Responses were durable; cCR was maintained ≥12 months in 98%. cCR12+pCR was 76%, with no recurrences at this analysis.
The safety profile was acceptable, manageable, and consistent with prior studies. Only2% discontinued due to adverse events.
cCR by investigator assessment is achieved earlier than by ICR. Assessment is challenging because ICR had access to sigmoidoscopy and MRI results only. This may contribute to the discrepancy between IRC and investigator-assessed responses. Dr. Cercek said for this patient-centric endpoint it’s absolutely necessary to have the patient present and a tumor board to discuss responses. Dr. Cercek and discussant David Tougeron, MD, agreed that better tools are needed to assess cCR.
AZUR-1 demonstrates sustained clinical responses after dostarlimab monotherapy in dMMR/MSI-H LARC, which has the potential to eliminate the need for chemotherapy, radiation, and surgery in a large proportion of patients.
On October 19, 2026, the US FDA granted accelerated approval to dostarlimab, 4 months ahead of the goal date, for adults with Stage II/III LARC that is MSI-H or dMMR, as determined by an FDA-authorized test for solid tumors.
Dr. Tougeron, MD, said that European regulators might be reluctant to approve dostarlimab treatment without data from a randomized trial, acknowledging that a randomized comparison to chemotherapy, surgery, and radiotherapy would raise ethical concerns. He said longer follow-up is needed, as well as QoL data.
