The FDA grants accelerated approval to Jemperli for MSI-H/dMMR locally advanced rectal cancer, based on sustained responses in the AZUR-1 trial.
Written By: Sravani Pamanji, PharmD
Reviewed By: Pharmacally Editorial Team
On October 19, 2026, the US Food and Drug Administration (FDA) granted accelerated approval to JEMPERLI® (dostarlimab-gxly), developed by GSK, for adults with previously untreated stage II or III locally advanced rectal cancer whose tumours are microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), as confirmed by an FDA-authorized test. The approval introduces a biomarker-directed treatment option that may allow selected patients to avoid additional cancer-directed interventions.
Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that helps the immune system recognise and attack cancer cells. MSI-H/dMMR tumours have defects in their DNA repair mechanisms, allowing genetic errors to accumulate and potentially making them more responsive to immunotherapy. This biological characteristic provides the rationale for using dostarlimab in this patient population.
AZUR-1: Evidence Behind the Approval
The approval was based on interim findings from AZUR-1, a global, open-label, single-arm phase II trial involving 154 patients with previously untreated stage II or III MSI-H/dMMR locally advanced rectal cancer.
Patients received up to nine doses of dostarlimab, administered intravenously every three weeks over six months. The study evaluated whether immunotherapy alone could produce sustained clinical complete responses and reduce the need for chemotherapy, radiation therapy and surgery. Its primary efficacy endpoint was a clinical complete response sustained for 12 months (cCR12), assessed by independent central review.
The investigator-assessed results showed that 68% of evaluable patients (98/144; 95% confidence interval [CI], 60%–76%) achieved cCR12. By independent central review, 47% of evaluable patients (54/116; 95% CI, 37%–56%) achieved the same endpoint. An additional 38 patients had achieved a clinical complete response but had not yet completed the required 12-month follow-up.
The two response rates reflect different assessment methods and evaluable populations, so they should be interpreted separately. The primary endpoint assessed by independent central review remains particularly important when evaluating the evidence supporting the approval.
Sustained Responses and the Potential to Avoid Surgery
Beyond the primary endpoint, GSK reported an exploratory analysis in which 76% of evaluable patients (110/144; 95% CI, 69%–83%) had no evidence of cancer one year or more after treatment. This included 98 patients who achieved a clinical complete response without surgery and 12 whose complete response was confirmed through pathological examination after surgery.
The FDA also reported that almost three-fourths of patients had not required surgery, radiation therapy or chemotherapy after treatment with Jemperli. GSK reported that 110 of the 154 treated patients received dostarlimab alone, required no additional treatment and had no disease progression at the reported data cutoff. No disease recurrences had been reported among responders after a median follow-up of more than two years.
These findings are encouraging for patients who might otherwise face treatment-related effects on bowel, urinary and sexual function, fertility and quality of life. However, the results do not mean that every patient can avoid conventional treatment or that the risk of recurrence has been eliminated. Longer follow-up is needed to establish the durability of these responses.
Safety Profile: What Patients Should Know
The safety profile of Jemperli in AZUR-1 was generally consistent with its established profile across solid tumours. Serious adverse reactions occurred in 20% of patients. The most common adverse reactions were fatigue (32%), rash (22%), diarrhoea (18%) and pruritus, or itching (17%). Treatment was permanently discontinued because of adverse reactions in 3% of patients.
The FDA highlighted the risk of immune-mediated adverse reactions, infusion-related reactions, complications associated with allogeneic haematopoietic stem cell transplantation and embryo-fetal toxicity. Immune-mediated reactions can affect healthy organs and tissues and may be severe or fatal. Appropriate monitoring is therefore essential during treatment. [1]
Although Jemperli may help selected patients avoid the complications associated with other cancer-directed interventions, immunotherapy also carries important risks. Its benefits must be considered alongside potential toxicities and the need for continued clinical assessment.
Regulatory Significance
The accelerated approval provides a new treatment option for adults with a defined biomarker profile. Jemperli received FDA Fast Track and Breakthrough Therapy designations for this indication, and its application was granted Priority Review. The FDA also reviewed the application through its National Priority Voucher pilot programme, completing the review ahead of the original target date.
Because the approval is based on interim findings, continued patient follow-up is important to establish whether the observed responses translate into lasting clinical benefit. The single-arm design of AZUR-1 also limits direct comparisons with conventional treatment because the trial did not include a randomised control group.
Clinical Interpretation
AZUR-1 supports dostarlimab monotherapy as a promising treatment option for eligible adults with previously untreated stage II or III MSI-H/dMMR locally advanced rectal cancer. The investigator-assessed cCR12 rate of 68% and independent central review rate of 47%, alongside the exploratory finding that 76% of evaluable patients had no evidence of cancer one year or more after treatment, highlight its potential for sustained disease control.
Of particular clinical interest is the possibility that selected patients may avoid surgery, chemotherapy and radiation therapy, reducing the burden of conventional treatment. However, these findings do not establish a cure or eliminate recurrence risk. Confirmatory biomarker testing, careful response assessment, adverse reaction monitoring and long-term surveillance remain essential. Further follow-up will help establish response durability and clarify which patients are most likely to benefit.
References
GSK plc. Jemperli (dostarlimab) approved in US as first and only immunotherapy for adults with MSI-H/dMMR locally advanced rectal cancer. October 19, 2026.
US Food and Drug Administration (FDA). FDA Approves Immunotherapy That May Allow Certain Patients with Rectal Cancer to Avoid Chemotherapy, Radiation and Surgery. October 19, 2026.
About the Writer
Sravani Pamanji is a PharmD (LinkedIn) professional with experience in scientific writing, medical literature review, drug profile preparation, and clinical case documentation. She has contributed to scientific publication and presented at the 74th Indian Pharmaceutical Congress. Her training includes ICH GCP E6(R3), scientific research, and medication safety. She is passionate about evidence-based medical communication and accurate dissemination of clinical and pharmaceutical information.