FDA Advisory Committee votes in support of trials designed to evaluate Jemperli as a potential treatment for mismatch repair-deficient/microsatellite instability-high locally advanced rectal cancer.- Glaxo Smith KLine

Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK, said: “The Committee’s positive vote in favour of our proposed clinical trial programme for dostarlimab reinforces our plans to generate data in support of a future US regulatory submission for the potential treatment of patients with dMMR/MSI-H locally advanced rectal cancer, a patient population with significant unmet medical needs and a standard of care that results in serious quality of life concerns. We thank the committee for the constructive dialogue and we look forward to continued interactions with FDA as we progress our development programme.”

The current standard of care (SoC) for patients with dMMR/MSI-H locally advanced rectal cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy. Neoadjuvant CRT provides local tumour control in most patients, but nearly one-third ultimately die from distant metastasis. Additionally, SoC is associated with long-term adverse effects, including bowel, urinary and sexual dysfunction, secondary malignancy and infertility .

As part of its proposed clinical trial programme, GSK is initiating a global, open-label, phase II clinical trial to investigate the efficacy and safety of dostarlimab-gxly as monotherapy – as a replacement for chemotherapy, radiation and/or surgery – for treatment-naïve patients with dMMR/MSI-H locally advanced rectal cancer. The primary endpoint of GSK’s proposed trial is clinical complete response for 12 months (cCR12) as assessed by Independent Central Review. Key secondary endpoints will include cCR for 36 months and event-free survival for three years by investigator assessment. In addition, the trial aims to confirm results generated in a separate ongoing investigator-initiated trial by researchers at Memorial Sloan Kettering Cancer Center (MSK). Researchers at MSK shared these findings in a late-breaking presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting with simultaneous publication in The New England Journal of Medicine. GSK intends to use data from the Company’s proposed trial, alongside data from MSK’s ongoing trial of 30 patients, to support a supplemental Biologics License Application (sBLA) for accelerated regulatory approval in this indication.

In January 2023, the FDA granted dostarlimab-gxly Fast Track designation for the treatment of dMMR/MSI-H locally advanced rectal cancer. Fast Track designation is designed to accelerate the development and expedite the review of potential new medicines to treat serious conditions with unmet medical needs. In addition, the application could be eligible for priority review if supported by clinical data at the time of the submission to the FDA.

See- Cercek A, Lumish MA, Sinopoli JC, et al. "PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer". N Engl J Med. Published online June 5, 2022. doi:10.1056/NEJMoa2201445.