PHILADELPHIA, PA — The U.S. Food and Drug Administration has granted accelerated approval to GSK’s Jemperli as a standalone treatment for certain patients with locally advanced rectal cancer, creating an alternative to chemotherapy, radiation and surgery for a genetically defined group of patients.
The approval covers adults with stage II or III rectal cancer whose tumors are microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), genetic characteristics found in approximately 5% to 10% of rectal cancers.
GSK (NYSE: GSK) said Jemperli, also known as dostarlimab-gxly, is the first immunotherapy approved in the United States for this specific patient population.
The decision follows results from AZUR-1, a phase II clinical trial in which a substantial proportion of patients had no detectable signs of cancer for at least 12 months after treatment.
According to investigator assessments, 68% of evaluable patients, or 98 of 144, achieved a clinical complete response sustained for 12 months without surgery. The 95% confidence interval was 60% to 76%.
An exploratory analysis found that 76%, or 110 of 144 evaluable patients, had no evidence of cancer at least one year after treatment. That group included 12 patients whose complete responses were confirmed through examination of tissue removed during surgery.
No disease recurrences had been reported among responders after a median follow-up exceeding two years, although the trial’s results continue to mature.
Independent central review, which is used to assess the study’s primary endpoint, showed a lower confirmed response rate at the interim analysis.
That review found that 47% of evaluable patients, or 54 of 116, had achieved a clinical complete response sustained for 12 months. Another 38 participants had already achieved a clinical complete response but had not yet completed the required follow-up period.
The distinction between investigator assessments and independent review remains important as additional trial data become available.
AZUR-1 enrolled 154 previously untreated patients in a global, open-label, single-arm study. Participants received nine intravenous doses of Jemperli over six months, with 500 milligrams administered every three weeks.
The trial evaluated whether the immunotherapy could produce sustained responses without the chemotherapy, radiation and surgery typically used to treat locally advanced rectal cancer.
Those conventional treatments can have lasting consequences, including bowel, urinary and sexual dysfunction, infertility and secondary cancers.
Jemperli blocks the programmed death receptor-1, or PD-1, a protein involved in regulating immune responses. Tumors with MSI-H or dMMR characteristics have defects in DNA repair that can make them particularly responsive to this type of immunotherapy.
Dr. Andrea Cercek, the AZUR-1 principal investigator and a colorectal cancer specialist at Memorial Sloan Kettering Cancer Center, said the approval provides access to a treatment selected according to tumor biology.
“The AZUR-1 results demonstrate the potential for a fundamentally different treatment approach in this biomarker-defined patient population,” Cercek said.
The treatment also carries safety risks.
Serious adverse reactions occurred in 20% of patients receiving Jemperli. The most frequently reported adverse reactions were fatigue in 32% of patients, rash in 22%, diarrhea in 18% and itching in 17%.
Three percent of patients permanently discontinued treatment because of adverse reactions.
The FDA granted the indication accelerated approval, a regulatory pathway that permits earlier authorization based on evidence considered reasonably likely to predict clinical benefit. Continued approval may depend on verification of that benefit in subsequent clinical studies.
The application previously received Fast Track and Breakthrough Therapy designations, Priority Review and a National Priority Voucher, which GSK said contributed to an approval ahead of its scheduled regulatory decision date.
The supplemental biologics license application is also being reviewed through Project Orbis, an FDA initiative coordinating oncology drug reviews with international regulatory authorities. Reviews remain underway in participating countries.
Michael Sapienza, chief executive officer of the Colorectal Cancer Alliance, emphasized the importance of identifying eligible patients through testing.
“Biomarker testing at diagnosis will be essential to identifying patients who may be eligible for this treatment and helping them understand their options,” Sapienza said.
GSK is responsible for developing, manufacturing and commercializing Jemperli. The drug was originally discovered by AnaptysBio and licensed to TESARO under a 2014 agreement.
The company is also studying Jemperli alone and in combination with other treatments for gynecologic, colorectal, head and neck, and other cancers.
The FDA decision expands the drug’s role in cancer treatment while introducing a potential treatment approach that could allow some patients with MSI-H/dMMR locally advanced rectal cancer to avoid the long-term effects of conventional therapy.
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