GSK has reported positive interim results from AZUR-1, a registrational phase 2 trial evaluating dostarlimab (Jemperli) monotherapy in patients with stage II/III mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) locally advanced rectal cancer. The single-arm trial met its primary endpoint, demonstrating a meaningful rate of sustained clinical complete response at 12 months (cCR12).¹
The July 13, 2026, announcement raises the possibility that dostarlimab could become the first immunotherapy to spare some patients in this biomarker-defined population from chemotherapy, radiation, and surgery, which are interventions associated with substantial long-term morbidity.¹
Key facts
- Drug: dostarlimab (Jemperli), PD-1 inhibitor
- Indication: dMMR/MSI-H rectal cancer, stage II/III
- Trial: AZUR-1, phase 2, single-arm (n=154)
- Primary endpoint: cCR12 (sustained CR at 12 mo) was met
- Safety: consistent with known profile; no new signals
- Regulatory status: not approved for rectal cancer
- Next step: data submission to FDA, other authorities
"The AZUR-1 results support the potential for dostarlimab to transform treatment for dMMR/MSI-H locally advanced rectal cancer," said Hesham Abdullah, MD, senior vice president, global head oncology, R&D, at GSK, in a company press release.¹ "These data demonstrate that some patients may be able to avoid those interventions while remaining free of detectable signs of cancer."
What did the AZUR-1 trial evaluate?
AZUR-1 is a global, open-label, single-arm trial that enrolled 154 participants with stage II/III dMMR/MSI-H locally advanced rectal cancer. Participants received 9 cycles of dostarlimab, administered as a 500-mg intravenous infusion every 3 weeks over 6 months. The primary objective, cCR12, was designed to determine whether dostarlimab monotherapy could allow patients to forgo chemoradiation and surgery entirely.
GSK reported that the interim safety profile was consistent with dostarlimab's established profile across solid tumors, with no new safety signals identified. The company plans to share interim data with global regulators, including for accelerated review in the United States, with full results expected at a future scientific congress.¹
Why does treatment burden matter in this population?
Rectal cancer affects an estimated 730,000 people worldwide annually, with the dMMR/MSI-H subtype accounting for roughly 5% to 10% of cases.¹ Standard treatment, such as neoadjuvant chemotherapy, radiation, and surgery, is often curative but can leave patients with permanent colostomies, urinary and sexual dysfunction, and infertility.2 This subtype is also known to respond poorly to conventional chemotherapy, making biomarker-driven alternatives clinically relevant.3
How does dostarlimab work, and where else is it used?
Dostarlimab is a programmed cell death protein 1 (PD-1)-blocking antibody that restores T-cell activity against dMMR/MSI-H tumors, which typically carry a high mutational burden. It first received FDA accelerated approval in April 2021 for dMMR endometrial cancer, was expanded to other dMMR solid tumors later that year, and gained additional endometrial cancer approvals in 2023 and 2024.⁴
Dostarlimab is not currently approved anywhere for rectal cancer. AZUR-1 builds on earlier, smaller research conducted with Memorial Sloan Kettering Cancer Center, which first demonstrated complete clinical responses using dostarlimab alone in this population.1
How should clinicians weigh these interim results?
The reported cCR12 rate represents a substantial improvement over historical complete-response rates with standard neoadjuvant therapy in this chemotherapy-resistant subtype.²,³ However, AZUR-1 is single-arm and non-randomized, without a concurrent chemoradiation comparator. GSK has not yet released detailed response, duration, or organ-preservation data. Whether cCR12 translates into durable long-term avoidance of surgery, the outcome of which is most relevant to patients, remains to be established.
What questions remain unanswered?
Patient-level efficacy and safety tables have not been published, which limits independent analysis ahead of peer-reviewed presentation. The single-arm design constrains causal comparison with standard care, and interim 12-month data typically require longer follow-up to confirm durability. Regulatory review, including a potential US accelerated pathway, is pending.¹
References
- GSK. Jemperli (dostarlimab) achieves sustained clinical complete responses in dMMR/MSI-H locally advanced rectal cancer. Published July 13, 2026. Accessed July 13, 2026. https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-achieves-sustained-clinical-complete-responses-in-dmmrmsi-h-locally-advanced-rectal-cancer/
- Cercek A, Dos Santos Fernandes G, Roxburgh CS, et al. Mismatch repair-deficient rectal cancer and resistance to neoadjuvant chemotherapy. Clin Cancer Res. 2020;26(13):3271-3279. doi:10.1158/1078-0432.CCR-19-3728
- Cercek A, Lumish M, Sinopoli J, et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med. 2022;386(25):2363-2376. doi:10.1056/NEJMoa2201445
- Shukla S, Patel H, Chen S, Sun R, Wei L, Chen ZS. Dostarlimab in the treatment of mismatch repair deficient recurrent or advanced endometrial cancer. Cancer Pathog Ther. 2023 Oct 18;2(3):135-141. doi:10.1016/j.cpt.2023.10.003