Jemperli Trial Shows 100% Disease-Free Results in dMMR Rectal Cancer

GSK plc has revealed updated long-term results from a phase II study in collaboration with Memorial Sloan Kettering Cancer Center (MSK), showcasing Jemperli (dostarlimab-gxly) as a pioneering first-line treatment for mismatch repair deficient (dMMR) locally advanced rectal cancer. This breakthrough treatment demonstrated a 100% clinical complete response (cCR) in 42 patients, meaning no detectable tumors post-treatment, as confirmed by MRI, endoscopy, and digital rectal exams. For the first 24 patients evaluated, the response was sustained with a median follow-up of approximately 26.3 months.

These findings were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The latest data builds upon preliminary results presented at ASCO 2022 and published in The New England Journal of Medicine. Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, highlighted the significance of these results, noting the potential of dostarlimab-gxly in treating dMMR rectal cancer without surgery.

Standard care for dMMR/microsatellite instability-high (MSI-H) rectal cancer typically involves chemotherapy and radiation, followed by surgery to remove the tumor. This approach, while effective initially, can lead to severe side effects and significantly impact quality of life. Nearly one-third of patients eventually succumb to metastatic cancer. Adverse effects from the current standard treatment include bowel, urinary, and sexual dysfunction, secondary cancers, and infertility.

Andrea Cercek, MD, from MSK, emphasized the potential of dostarlimab-gxly in avoiding these detrimental outcomes. She expressed optimism about this new treatment paradigm for dMMR rectal cancer, noting the durable complete tumor regression observed without the need for conventional, life-altering treatments.

The safety profile of dostarlimab-gxly was consistent with known data, with no grade 3 or higher adverse events reported during the trial. Although dostarlimab-gxly is not yet approved for the frontline treatment of locally advanced dMMR rectal cancer, GSK is advancing its evaluation through the AZUR clinical trial program. AZUR-1, a global phase II registrational trial, is assessing the efficacy and safety of dostarlimab-gxly as a monotherapy for treatment-naïve patients with dMMR/MSI-H locally advanced rectal cancer. The aim is to validate the findings from Dr. Cercek's study at MSK. AZUR-2, a phase III trial, is comparing the efficacy of perioperative dostarlimab-gxly against the standard care in untreated T4N0 or Stage III dMMR/MSI-H colon cancer.

Mismatch repair deficient (dMMR) rectal cancer, a subset of colorectal cancer, affects approximately 5-10% of rectal cancer patients. This condition involves abnormalities in the DNA repair process, making it a predictive biomarker for response to immune checkpoint inhibitors like PD-1 therapy. These abnormalities are common in various cancers, including endometrial and other gastrointestinal cancers.

Jemperli, an anti-PD-1 therapy, works by binding to the PD-1 receptor and blocking its interaction with PD-1 ligands, thus enhancing the immune system's ability to target and destroy cancer cells. Discovered by AnaptysBio, Inc. and subsequently licensed to TESARO, Inc., Jemperli is now being developed and commercialized by GSK.

While Jemperli shows promise for treating advanced dMMR rectal cancer, it is crucial to monitor for immune-mediated adverse reactions, which can be severe or fatal. These reactions may affect any organ system and require prompt medical intervention. Continuous evaluation and appropriate management of adverse reactions are essential to ensure patient safety during treatment.

GSK remains committed to advancing oncology treatments, focusing on hematologic malignancies, gynecologic cancers, and other solid tumors through innovative immuno-oncology and tumor-targeting therapies. The company aims to improve patient survival rates and overall quality of life by exploring new therapeutic options and expanding the potential applications of existing treatments like Jemperli.