Accelerated approval for dostarlimab-gxly (Jemperli) pairs a single-arm phase 2 dataset with an FDA-authorized biomarker test and confirmatory requirements.
The FDA has granted accelerated approval to Jemperli (dostarlimab-gxly), a programmed death receptor-1 (PD-1) blocking antibody, for adults with stage II and III microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) locally advanced rectal cancer, GSK announced Oct. 19.1
The approval rests on a single-arm phase 2 trial in a biomarker-defined population.1 The decision is notable for its construction: a sustained clinical response endpoint, patient selection through an FDA-authorized test, and an application that was approved ahead of its scheduled action date.1
Tony Wood, chief scientific officer at GSK, said: “Today, Jemperli becomes the first and only approved immunotherapy for adults in the US with MSI-H/dMMR locally advanced rectal cancer. For decades, treatment has relied on chemotherapy, radiation and surgery. This approval offers a new treatment approach and represents an important step towards more personalized care for these patients.”1
The antibody binds the PD-1 receptor and blocks its interaction with the receptor’s two ligands.2 Tumors with MSI-H/dMMR status cannot properly repair DNA damage, and the resulting accumulation of mutations often makes them responsive to immunotherapy.1
The biomarker appears in about 5% to 10% of rectal cancers.1 AnaptysBio discovered the antibody and licensed it to Tesaro in 2014. GSK is now responsible for its research, development, commercialization and manufacturing.1
The product is already approved for endometrial cancer and for previously treated dMMR solid tumors.1
AZUR-1 is a global, open-label, single-arm phase 2 trial of 154 patients with previously untreated stage II or III disease. Participants received nine cycles of a 500 mg intravenous infusion every three weeks over six months.1
The primary objective was clinical complete response sustained for 12 months, assessed by independent central review. Those data are still maturing: 47% of 116 evaluable patients (95% confidence interval, 37% to 56%) have reached the milestone.1
Investigator-assessed data showed 68% of 144 evaluable patients (95% confidence interval, 60% to 76%) reached 12 months. An exploratory analysis found 76% had no evidence of cancer a year or more after treatment, including 12 patients whose response was confirmed by tissue analysis after surgery.
No recurrences have been reported among responders after a median follow-up of more than two years.1 Serious adverse reactions occurred in 20% of patients, and 3% discontinued because of adverse reactions.1
A Memorial Sloan Kettering Cancer Center phase 2 study of single-agent dostarlimab, which planned chemoradiotherapy and surgery afterward, found clinical complete response in all 12 patients in its initial report, with no adverse events of grade 3 or higher.3
The label states that approval is based on sustained clinical complete response for 12 months, that the long-term risk of relapse is unknown, and that continued approval may depend on confirmatory trials.1 In 2023, an FDA advisory committee voted 8 to 5 that two proposed single-arm trials could be sufficient to characterize the drug’s benefits and risks in this setting.
The trial plan named clinical complete response at 36 months and three-year event-free survival as key secondary endpoints.2 The approval announcement does not report them.1
The indication also received Fast Track and Breakthrough Therapy designations, priority review and a national priority voucher, and is under review through Project Orbis, which allows concurrent review by international authorities.1 FDA acted ahead of the February 2027 action date it assigned in August.4
The indication requires an FDA-authorized test.1 Michael Sapienza, chief executive officer of the Colorectal Cancer Alliance, said: “People facing rectal cancer are often thinking not only about treating their disease, but also worrying about what life will look like afterwards. The possibility of avoiding chemotherapy, radiation and surgery represents a meaningful advance for patients and their families. Biomarker testing at diagnosis will be essential to identifying patients who may be eligible for this treatment and helping them understand their options.”1
Dr. Andrea Cercek, AZUR-1’s principal investigator and section head of colorectal cancer at Memorial Sloan Kettering Cancer Center, said: “The AZUR-1 results demonstrate the potential for a fundamentally different treatment approach in this biomarker-defined patient population, and today’s approval means MSI-H/dMMR patients can now access a licensed treatment tailored to the biology of their disease.”1
The release discloses that Cercek has financial interests related to GSK.1 AZUR-1 has no control arm, and the independent-review result designated as the primary objective is lower and less mature than the investigator-assessed figure.
Longer follow-up and confirmatory evidence will determine whether responses prove durable. Full interim data are scheduled for presentation at the European Society for Medical Oncology Congress in October 2026.1
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