Jemperli▼ (dostarlimab) becomes the first immunotherapy treatment to receive NICE recommendation for use, in line with its license, in eligible endometrial cancer patients in first line setting

Jemperli▼ (dostarlimab) becomes the first immunotherapy treatment to receive NICE recommendation for use, in line with its license, in eligible endometrial cancer patients in first line setting

• This final draft guidance recommends the use of dostarlimab in combination with platinum-containing chemotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy.[i]
• Following a positive recommendation from the National Institute for Health and Care Excellence (NICE), approximately 580 patients in England, Wales and Northern Ireland could be eligible for treatment with dostarlimab.[ii]
• Endometrial cancer is the UK's most common gynaecological cancer, with rising incidence and mortality rates.[iii]^,[iv],[v]

GSK plc (LSE/NYSE: GSK) today announced that the National Institute for Health and Care Excellence (NICE) has published a final draft guidance recommending the use of dostarlimab in combination with platinum-containing chemotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy. In England, Wales and Northern Ireland, there are approximately 2,770 people diagnosed with advanced or recurrent disease each year, of which approximately 580 will now be eligible for treatment with dostarlimab.ⁱⁱ

Dr Rebecca Kristeleit, Consultant Medical Oncologist, Guy's and St Thomas' NHS Foundation Trust and Adjunct Reader, King’s College London, said: “NICE’s recommendation for use of dostarlimab in combination with chemotherapy in the first line treatment of dMMR endometrial cancer enables access to the first major advance in decades for women with this disease with the potential to significantly improve their survival. This treatment option heralds a new era for biomarker-directed treatment of advanced endometrial cancer.”

Endometrial cancer, a form of uterine cancer that starts in the lining of the endometrium (womb), is the most common gynaecological cancer in the UK, with rising incidence and mortality rates.^iii,iv,v Over the last decade in the UK (between 2006-2008 and 2016-2018), uterine cancer age standardised incidence rates for females increased by 12%.^v Despite advances in medical science, outcomes of advanced and recurrent endometrial cancer remain poor.[vi]

The median overall survival of people with recurrent, advanced endometrial cancer is reported to be less than three years when treated with standard of care platinum-based chemotherapy.[vii] Based on survival statistics for patients diagnosed between 2013 and 2017 in England, only 15% of people diagnosed with stage 4 disease survive for five years or longer.[viii]

Dr Chloe Barr, Specialist Registrar, Trustee and Advocacy Lead at Peaches Womb Cancer Trust, said: “This new treatment for primary advanced or recurrent dMMR/MSI-H endometrial cancer will provide options for people currently facing the reality of very few effective anti-cancer treatments. This decision is very welcome news and we hope that this is just the first step towards wider availability of more effective first-line treatment options for those affected by this devastating cancer.”

Jack Harris, Vice-President UK Oncology, GSK, said: “At GSK, we aspire to get ahead of cancer and improve outcomes for people living with the devastating reality of a diagnosis. Today’s decision is an important step forward, and a testament to our ongoing commitment to driving innovation for people with unmet needs, providing patients with the opportunity to access this treatment in the first line treatment setting. While today’s news is specific to endometrial cancer, our commitment in oncology extends to difficult to treat solid tumours and haematological malignancies. We have seen great developments within our pipeline over the last year and we are proud to have contributed to meaningful advancements in oncology”.

Following the NICE decision, GSK is working with relevant health authorities across the UK, including Scotland, where this medicine is being assessed by the Scottish Medicine Consortium, to try to provide access for those who may benefit from the therapy in this first line setting. Dostarlimab has been accessible in the UK since 2022, as monotherapy for treatment of adult patients with dMMR/ MSI-H recurrent or advanced endometrial cancer following prior platinum based chemotherapy, available on the NHS in England via the Cancer Drugs Fund (CDF).[ix]

About endometrial cancer

Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynaecological cancer in developed countries, with approximately 420,000 new cases reported worldwide in 2022.[x]

About dostarlimab[xi]

Dostarlimab is indicated:

• in combination with platinum-containing chemotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/ microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy as a monotherapy for the treatment of adult patients with dMMR/ MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.
• as monotherapy for the treatment of adult patients with dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.

The Great Britain Marketing Authorisation granted by the Medicines and Healthcare Products Regulatory Agency (MHRA) was based on pivotal data from Part 1 of the Phase 3 randomised, double-blind RUBY study, which evaluated dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer.

About RUBY Part 1^vii

RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. The dual-primary endpoints in Part 1 are investigator-assessed progression-free survival (PFS) based on the Response Evaluation Criteria in Solid Tumours v1.1 and overall survival (OS). The statistical analysis plan included pre-specified analyses of PFS in the dMMR/MSI-H and intent-to-treat (ITT) populations and OS in the overall population. Pre-specified exploratory analyses of PFS in the mismatch repair proficient (MMRp)/microsatellite stable (MSS) population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma.

Secondary endpoints in Part 1 include PFS per blinded independent central review, overall response rate, duration of response, disease control rate, time to second objective disease progression (PFS2), patient-reported outcomes, and safety and tolerability. The safety and tolerability profile of dostarlimab in combination with carboplatin-paclitaxel in the RUBY phase III trial was generally consistent with the known safety profiles of the individual agents. Adverse events of any grade occurring in >20% of the overall population in either arm were fatigue, alopecia, nausea, peripheral neuropathy, anaemia, arthralgia, constipation, diarrhoea, myalgia, hypomagnesaemia, peripheral sensory neuropathy, decreased appetite, dyspnoea and rash. Any ≥grade 3 treatment emergent adverse events(TEAE) and any serious adverse event were approximately 10% higher in the dostarlimab plus carboplatin-paclitaxel arm, compared with the placebo plus carboplatin-paclitaxel arm, in the overall population. The incidence of grade 3 or higher adverse events was 170 (70.5%) patients in the treatment arm compared to 147 (59.8%) in the control arm. Serious adverse events occurred in 91 (37.8%) patients in the treatment arm compared to 68 (27.6%) in the control arm.

Refer to the dostarlimab Summary of Product Characteristics (SmPC) for a full list of adverse events and the complete important safety information.^xi

GSK in oncology

GSK is committed to maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, tumour cell targeting therapies and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, and antibody-drug conjugates, either alone or in combination.

About GSK

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.

[i] NICE Final Draft Guidance. Data on file. REF-222937

[ii] GSK Data on file. REF-218017

[iii] NIH. Rising Endometrial Cancer Rates Spur New Approaches to Prevention. Available at: https://prevention.cancer.gov/news-and-events/blog/rising-endometrial-cancer-rates-spur-new-approaches-prevention. Last accessed March 2024.

[iv] The Royal Marsden NHS Foundation Trust. Q&A: Gynaecological cancers. Available at: https://www.royalmarsden.nhs.uk/gp-update/qa-gynaecological-cancers. Last accessed March 2024.

[v] Cancer Research UK. Uterine cancer statistics. Available at https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/uterine-cancer#heading-One. Last accessed March 2024.

[vi] Oaknin A, et al. Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(9):860–877.

[vii] Mirza MR, et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-2158. doi: 10.1056/NEJMoa2216334.

[viii] Cancer Research UK. Womb cancer survival. Available at: https://www.cancerresearchuk.org/about-cancer/womb-cancer/survival. Last accessed March 2024.

[ix] NICE. Dostarlimab for previously treated advanced or recurrent endometrial cancer with high microsatellite instability or mismatch repair deficiency. Available at: https://www.nice.org.uk/guidance/ta779. Last accessed. Last accessed March 2024.

[x] World Health Organisation International Agency for Research on Cancer (IARC). GLOBOCAN 2024: Corpus Uteri Factsheet. Available at: https://gco.iarc.fr/today/en/dataviz/tables?mode=population&cancers=24. Last accessed March 2024

[xi] Dostarlimab Summary of Product Characteristics. Great Britain.