Published: Feb 08, 2023
By Tristan Manalac
The FDA has set a Feb. 9 meeting for its Oncologic Drugs Advisory Committee (ODAC) to discuss whether GSK’s clinical development plans for Jemperli (dostarlimab) could support accelerated approval.
Jemperli is an IgG4 humanized monoclonal antibody blocking the PD-1 receptor. The drug is approved for use in mismatch repair-deficient (dMMR) endometrial cancer and dMMR recurrent or advanced solid tumors.
GSK is now hoping to expand Jemperli’s label to include treatment-naïve dMMR locally advanced rectal cancer (LARC). For this, the company is proposing two single-arm trials. The first, a single-center study, is set to enroll 30 patients, while the second will recruit 100 patients across several study sites.
In both trials, patients will be treated with 500 mg intravenous Jemperli every three weeks for nine cycles.
Jemperli’s efficacy will primarily be evaluated as the 12-month clinical complete response rate (cCR), a composite of no residual disease by endoscopy or rectal-specific MRI and no evidence of metastatic disease one year after the first cCR evaluation.
GSK plans to use cCR results as the clinical endpoint to support a supplemental Biologics License Application for Jemperli’s accelerated approval in this indication.
To verify the clinical benefit of Jemperli in this patient population, the company also plans to evaluate cCR and event-free survival after three years of follow-up. GSK also proposes to include a randomized controlled trial comparing Jemperli against the standard of care in Stage II/III dMMR colon cancer as supportive confirmatory evidence.
FDA Red Flags
Previously, Jemperli had already shown its promise in gastric cancer when it elicited a 100% cCR in a June 2022 study. With just 12 patients completing treatment, Alan P. Venook, M.D., colorectal cancer physician, University of California, San Francisco, called the study “unheard-of.”
The FDA appears to be skeptical, however.
In its briefing documents published before the ODAC meeting, the regulatory body flagged “the unprecedented use of cCR as the major endpoint to support an approval in oncology.”
In particular, the agency pointed out that there are currently no evidence-based guidelines to support the use of cCR as an efficacy metric in clinical practice or clinical trials.
“The use of cCR in LARC clinical decision-making is based on small, mostly retrospective, uncontrolled studies that vary in design” and other factors such as treatment regimen and monitoring protocol, the FDA wrote.
The agency is also asking for expert input regarding the appropriateness of GSK’s single-arm trial designs and the proposed confirmatory data to support Jemperli’s clinical benefit.