FDA Grants Breakthrough Therapy Designation to GSK’s Jemperli for Locally Advanced Mismatch Repair Deficient/Microsatellite Instability-High Rectal Cancer

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The FDA has granted Breakthrough Therapy Designation (BTD) to GSK’s Jemperli for treating locally advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer. According to the company, the BTD is based on results from a Phase II collaborative study with Memorial Sloan Kettering Cancer Center, in which all patients treated with Jemperli demonstrated a clinical complete response (cCR).¹

“Today’s designation, which is based on the unprecedented 100% clinical complete response rate of dostarlimab reported to date, supports a path to help change the treatment paradigm for patients with locally advanced dMMR/MSI-H rectal cancer, who face long-term adverse quality-of-life effects. Our registrational AZUR-1 trial is continuing to study dostarlimab in this patient population,” said Hesham Abdullah, SVP, global head oncology, R&D, GSK, in a press release.

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and stops its interaction with the PD-1 ligands PD-L1 and PD-L2. It has shown potential both as a monotherapy and in combination with standard of care and future novel cancer therapies, particularly in patients with currently limited treatment options, according to GSK.^2,3

The results from the collaborative study showed sustained cCR in the first 24 patients with a median follow-up of 26.3 months. Investigators defined 100% cCR as no evidence of tumors as assessed by magnetic resonance imaging, endoscopy, PET scan, and digital rectal exam. No adverse events of grade 3 or higher were reported from the trial.¹

According to statistics from the American Cancer Society, it is estimated that by the end of the year, there will be approximately 106,590 new cases of colorectal cancer in the United States, resulting in an estimated 46,220 deaths as a result. Since the mid-1980s, the diagnosis rate of colon or rectal cancer has dropped significantly, primarily because more people are getting screened and changing their lifestyle-related risk factors. However, rates have been increasing by 1% to 2% per year since the mid-1990s in people under 55 years of age.

Currently, colorectal cancer is the third highest third-leading cause of cancer-related deaths in men and the fourth leading cause in women in the United States. The American Cancer Society states that the drop in death rates over the past few decades could be a result of colorectal polyps being found more often by screening and removed before they can develop into cancers.⁴

“These findings demonstrate the potential of dostarlimab as a novel approach to treating locally advanced dMMR rectal cancer that leads to durable complete tumour regression without the need for life-altering treatment. As a clinician, I’ve seen firsthand the debilitating impact of standard treatment of dMMR rectal cancer and am thrilled about the potential of dostarlimab in these patients,” principal trial investigator Andrea Cercek, MD, section head, Colorectal Cancer, co-director, Center for Young Onset Colorectal and Gastrointestinal Cancer, MSK, said in a press release.³

Back in June, results from the study were first presented at the 2024 American Society of Clinical Oncology Annual Meeting.^2,3 Currently, the trial is evaluating enrolled patients, with GSK’s ongoing Phase II registrational AZUR-1 trial in locally advanced dMMR/MSI-H rectal cancer aiming to confirm the findings of the study. Jemperli has yet to be approved for frontline treatment in this indication by any global regulatory agency.¹

References

1. Jemperli (dostarlimab) receives US FDA Breakthrough Therapy Designation for locally advanced dMMR/MSI-H rectal cancer. GSK. December 16, 2024. Accessed December 16, 2024. https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-receives-us-fda-breakthrough-therapy-designation-for-locally-advanced-dmmrmsi-h-rectal-cancer/

2. Data Presented at ASCO Show Improved Complete Response with Jemperli as a First-Line Treatment for Locally Advanced Rectal Cancer in Patients with Mismatch Repair Deficient Status. PharmExec. June 3, 2024. Accessed December 16, 2024. https://www.pharmexec.com/view/data-presented-at-asco-show-improved-complete-response-with-jemperli-as-a-first-line-treatment-for-locally-advanced-rectal-cancer-in-patients-with-mismatch-repair-deficient-status

3. Jemperli (dostarlimab) trial continues to show unprecedented results with no evidence of disease in 100% of patients with locally advanced mismatch repair deficient (dMMR) rectal cancer. GSK. June 3, 2024. Accessed December 16, 2024. https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-trial-continues-to-show-unprecedented-results/

4. Key Statistics for Colorectal Cancer. American Cancer Society. Accessed December 16, 2024. https://www.cancer.org/cancer/types/colon-rectal-cancer/about/key-statistics.html#:~:text=The%20American%20Cancer%20Society's%20estimates,men%20and%2018%2C890%20in%20women)