The FDA ( US Food and Drug Administration ) has approved Jemperli ( Dostarlimab-gxly; Dostarlimab ), a programmed death receptor-1 ( PD-1 ) blocking antibody.
Dostarlimab is indicated for the treatment of adult patients with mismatch repair-deficient ( dMMR ) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that have progressed on or following prior treatment with a Platinum-containing regimen.
This indication is approved under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Around 1 in 4 women with endometrial cancer may experience a recurrence or be diagnosed with advanced disease. For women whose disease recurs after Platinum-based chemotherapy, there is generally no accepted standard of care.
Additionally, endometrial cancer has the highest rate of dMMR among tumour types at approximately 25%, and increased rates of recurrence have been reported for women with dMMR endometrial cancer.
The approval is based on results from the dMMR endometrial cancer cohort of the ongoing GARNET trial, a large, multicentre, non-randomised, multiple parallel-cohort, open-label study, representing the largest dataset to date evaluating an anti-PD-1 antibody as monotherapy treatment in women with endometrial cancer.
The primary endpoints in the GARNET trial were overall response rate ( ORR ) and duration of response ( DOR ) as assessed by blinded independent central review ( BICR ).
Results have shown an ORR of 42.3% ( 95% CI; 30.6-54.6 ) with a complete response ( CR ) rate of 12.7% and partial response rate ( PR ) of 29.6% among the 71 evaluable patients with dMMR advanced or recurrent endometrial cancer who had progressed on or after treatment with a Platinum-containing regimen.
Of those that responded, 93.3% demonstrated a DOR of 6 months or more. After a median follow-up of 14.1 months, the median duration of response was not reached ( 2.6-22.4+ ).
Patients received 500 mg of Dostarlimab as an intravenous infusion once every three weeks for four doses, followed by 1,000 mg once every six weeks until disease progression or unacceptable toxicity.
Among the 104 patients evaluable for safety, the most commonly reported adverse reactions ( occurring in 20% or more of patients ) were fatigue / asthenia ( 48% ), nausea ( 30% ), diarrhoea ( 26% ), anaemia ( 24% ) and constipation ( 20% ).
The most common grade 3 or 4 adverse reactions ( 2% or more ) were anaemia and transaminases increase.
Dostarlimab was permanently discontinued due to adverse reactions in 5 ( 4.8% ) patients.
No deaths attributed to dostarlimab were reported in the study.
Endometrial cancer is a main type of uterine cancer that forms in the inner lining of the uterus, known as the endometrium.
Endometrial cancer can be classified as mismatch repair-deficient / microsatellite instability-high ( dMMR/MSI-H ) or mismatch repair-proficient / microsatellite stable.
Nearly 60,000 new cases of endometrial cancer are expected in the US in 2021, making endometrial cancer the most common gynaecologic malignancy in the US.
Approximately 25% of women with endometrial cancer will be diagnosed with advanced disease or will experience a recurrence. ( Xagena )
Source: GSK, 2021