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GlaxoSmithKline Plc - FDA approves GSK's JEMPERLI (dostarlimab-gxly)

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GlaxoSmithKline Plc

FDA grants accelerated approval for GSK's JEMPERLI (dostarlimab-gxly) for women with recurrent or advanced dMMR endometrial cancer

  • GARNET study represents the largest dataset of anti-PD-1 monotherapy treatment of women with endometrial cancer
  • Study results showed an overall response rate of 42%  
  • 93% of responders had a duration of response of ≥6 months

GlaxoSmithKline plc (LSE/NYSE: GSK) today announced that the US Food and Drug Administration (FDA) has approved JEMPERLI (dostarlimab-gxly), a programmed death receptor-1 (PD-1) blocking antibody, based on the company's Biologics License Application. 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). 

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK, said: "Unfortunately, as many as 60,000 women are diagnosed with endometrial cancer in the US each year and these women currently have limited treatment options if their disease progresses on or after first-line therapy. Today's approval of dostarlimab by the FDA has the potential to transform the treatment landscape for these women and demonstrates our continued commitment to helping patients with gynaecologic cancers."

Around 1 in 4 women with endometrial cancer may experience a recurrence or be diagnosed with advanced disease.[i],[ii] For women whose disease recurs after platinum-based chemotherapy, there is generally no accepted standard of care.[iii],[iv],[v] Additionally, endometrial cancer has the highest rate of dMMR among tumour types[vi],[vii] at approximately 25%, vii   and increased rates of recurrence have been reported for women with dMMR endometrial cancer.[viii]

Dr Jubilee Brown, Professor and Division Director of Gynaecologic Oncology at Levine Cancer Institute, Atrium Health, and investigator on the GARNET study, noted: "The approval of dostarlimab has the potential to change the way we've been treating dMMR advanced or recurrent endometrial cancer after standard platinum-based chemotherapy, especially given the overall response rate and durability of response that we saw in the GARNET trial."

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. v The approval was granted under the FDA's Real-Time Oncology Review pilot programme, and dostarlimab was initially granted breakthrough therapy designation in May of 2019 for recurrent or advanced dMMR 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 showed 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%) 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.

Dr Sue Friedman, Executive Director of Facing Our Risk of Cancer Empowered (FORCE), commented: "We applaud GSK and their ongoing efforts to support women with endometrial cancer, the most common gynaecologic malignancy in the US and the sixth most common cancer in women worldwide. For many women whose disease is dMMR and has progressed after platinum-based chemotherapy, the approval of dostarlimab brings a new treatment option to an underserved patient population."

GSK is also studying dostarlimab for endometrial cancer in earlier treatment lines and in combination with other therapeutic agents for patients with advanced solid tumours or metastatic cancer as we work to expand our oncology pipeline and reinforce our portfolio of cancer treatments.