▎WuXiEdited by Kant Content Team

GSK announced today the updated long-term data from the Phase 2 clinical trial of its PD-1 inhibitor Jemperli (dostarlimab) as a first-line treatment replacing surgery for locally advanced rectal cancer with mismatch repair deficiency (dMMR). According to the press release,The trial was completed by 42 participants.JemperliAmong the treated patients, an "unprecedented" 100% clinical complete response rate (cCR) was observed. The first 24 evaluated patients showed sustained clinical complete response during a median follow-up period of 26.3 months.DetailedThe data was presented at the American Society of Clinical Oncology (ASCO) annual meeting this year. Other registrational trials of Jemperli for the treatment of dMMR/microsatellite instability-high (MSI-H) rectal and colorectal cancer (CRC) are currently recruiting patients.

Rectal cancer is a type of cancer that begins in the rectum (the last part of the large intestine) and is typically classified as a type of colorectal cancer. Colorectal cancer is the third most commonly diagnosed cancer in the world. Approximately 5-10% of rectal cancers are dMMR/MSI-H, meaning the cancer cells have mutations that affect the proper repair of DNA during cell replication.dMMR status is a biomarker that has been shown to predict response to immune checkpoint blockade therapies such as PD-1 antibodies.Common dMMR tumors include endometrial cancer, colorectal cancer, and other gastrointestinal cancers, but they may also occur in other solid tumors.

Current Standard of Care (SoC) for patients with dMMR/MSI-H locally advanced rectal cancer involves initial treatment with chemotherapy plus radiotherapy, followed by surgical resection of the tumor along with part of the intestine and/or surrounding tissues. While most patients initially respond positively to treatment, nearly one-third ultimately succumb to distant metastases of the cancer. Additionally, surgeries and chemoradiotherapy associated with SoC can lead to long-term adverse effects, significantly negatively impacting patients' quality of life, including bowel, urinary, and sexual dysfunction, secondary cancers, and infertility.

The AZUR-1 trial, which was recently announced, is a global, multi-center, open-label Phase 2 registration clinical trial.To investigate the efficacy and safety of Jemperli monotherapy as an alternative to chemotherapy, radiotherapy, and/or surgery in treatment-naïve patients with locally advanced dMMR/MSI-H rectal cancer.The analysis shows,The cCR was 100% in 42 patients who completed Jemperli treatment.cCR is defined as complete pathological remission or no tumor assessed by magnetic resonance imaging, endoscopy, and digital rectal examination. Additionally,Among the first 24 evaluable patients, sustained clinical complete response was observed during the median follow-up of 26.3 months (95% CI: 12.4-50.5).

The safety and tolerability profile of Jemperli is consistent with the known safety profile of the drug. No adverse events of grade 3 or higher were reported in this trial.

Jemperli is an antibody that binds to the PD-1 receptor and blocks its interaction with the ligands PD-L1 and PD-L2.Jemperli was approved in the U.S. in April 2021FDA Approval, as a monotherapy for dMMR advanced or recurrent endometrial cancer after prior platinum-based therapy. This treatment was also approved in July 2023.ApprovedIn combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer determined to be dMMR or MSI-H by an FDA-approved test. Additionally, Jemperli received FDA approval in August 2021.Accelerated ApprovalFor the treatment of patients with recurrent or advanced solid tumors carrying dMMR, whose dMMR status is confirmed by an FDA-approved test, whose disease continues to progress after receiving prior treatment, and for whom there are no other satisfactory alternative treatment options.

References:

[1] Jemperli (dostarlimab-gxly) trial continues to show unprecedented results with no evidence of disease in 100% of patients with locally advanced mismatch repair deficient (dMMR) rectal cancer. Retrieved June 3, 2024 from https://www.businesswire.com/news/home/20240602370374/en

[2] Durable complete responses to PD-1 blockade alone in mismatch repair deficient locally advanced rectal cancer. Retrieved June 3, 2024 from https://meetings.asco.org/abstracts-presentations/234205

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