On February 9th, the FDA’s Oncologic Drugs Advisory Committee (ODAC) will be discussing GSK’s Jemperli (dostarlimab) and its potential to receive accelerated approval for treatment of rectal cancer. It promises to be an exciting meeting as they explore the clinical development plans of the drug and its potential to make a positive impact on the lives of those suffering from this type of cancer.
Jemperli is a revolutionary breakthrough in cancer treatment, offering a unique solution to those battling with mismatch repair-deficient (dMMR) endometrial cancer and dMMR recurrent or advanced solid tumors. This IgG4 humanized monoclonal antibody works by blocking the PD-1 receptor, providing a much-needed treatment option for those affected.
GSK is looking to extend Jemperli’s label to include treatment-naïve dMMR LARC. To do this, they are proposing two single-arm trials. The first, a single-center study, will enroll 30 patients, while the second will enroll 100 patients across multiple sites. This could be a defining moment for Jemperli, as it could soon be used to treat a much wider range of cancers.
Patients in both trials will receive a powerful and innovative treatment regimen of 500 mg of Jemperli intravenously every three weeks for nine cycles. With this innovative approach, researchers are hopeful that they will be able to make a positive impact on the health of those involved.
Jemperli’s success rate will be closely monitored over the course of one year, with the primary goal of achieving a clinical complete response rate (cCR). This composite measure includes the absence of any residual disease by endoscopy or rectal-specific MRI, and no evidence of metastatic disease one year following the first cCR evaluation.
GSK is preparing to submit a supplemental Biologics License Application for Jemperli’s accelerated approval in this indication, bolstered by cCR results as the clinical endpoint.
GSK is taking steps to comprehensively assess the clinical benefit of Jemperli in this patient population. To do so, they will evaluate cCR and event-free survival after three years of follow-up, as well as conduct a randomized controlled trial comparing Jemperli against the standard of care in Stage II/III dMMR colon cancer to gather further supportive evidence. With these measures, GSK is aiming to ensure that Jemperli is as safe and effective as possible in this patient population.
FDA Red Flags
In June 2022, Jemperli made waves in the medical community with a groundbreaking study in gastric cancer. A remarkable 100% complete response rate was achieved in just 12 patients, achieving results that were previously unheard of. Alan P. Venook, M.D., a renowned colorectal cancer physician from the University of California, San Francisco, was among those to hail the study’s success.
The FDA doesn’t seem to be convinced, casting doubt on the situation.
Before the ODAC meeting, the regulatory body raised questions about the use of cCR (complete response rate) as the primary endpoint for approval of a cancer treatment – an unprecedented move in oncology.
The FDA has raised concerns about the use of cCR as an efficacy metric in clinical practice or clinical trials, noting that there is no evidence-based support for its use. With no established guidelines to follow, the potential implications of cCR remain uncertain.
Small, mostly retrospective and uncontrolled studies have been used to inform clinical decisions regarding cCR and LARC, but these studies vary in design, treatment regimen, and monitoring protocol. The FDA has noted that further research is needed to more effectively assess the efficacy of cCR in this context.
The FDA is seeking expert feedback on the suitability of GSK’s single-arm trial designs and the confirmatory data proposed to demonstrate the clinical benefit of Jemperli. It is interested in gathering insights on the best way to ensure the safety and efficacy of this new treatment.