REG - GSK PLC - Positive phase III RUBY results for Jemperli

GSKAnnouncement

28/03/2023 07:00

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RNS Number : 3877U  GSK PLC  27 March 2023

Issued: 27 March 2023, London UK

 

Phase III RUBY clinical trial demonstrates potential of Jemperli (dostarlimab)
plus chemotherapy to redefine the treatment of primary advanced or recurrent
endometrial cancer versus chemotherapy alone

·   72% and 36% reduction in the risk of disease progression or death
observed in the dMMR/MSI-H population and overall patient population,
respectively

·   Clinically meaningful overall survival trend observed at interim
analysis

·   Results presented in same-day presentations at ESMO Virtual Plenary and
SGO Annual Meeting and simultaneously published in The New England Journal of
Medicine

·   Regulatory submissions planned for the first half of 2023

 

GSK plc (LSE/NYSE: GSK) today announced interim results from Part 1 of the
RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial investigating Jemperli
(dostarlimab) plus standard-of-care chemotherapy (carboplatin-paclitaxel)
followed by dostarlimab compared to chemotherapy plus placebo followed by
placebo in adult patients with primary advanced or recurrent endometrial
cancer.

 

Hesham Abdullah, Senior Vice President, Global Head of Oncology Development,
GSK said: "These positive results from the RUBY trial bring us one step closer
to addressing the significant unmet needs of endometrial cancer patients and
add to the growing body of evidence on dostarlimab, strengthening our belief
in its potential to transform cancer treatment as a backbone immuno-oncology
therapy."

 

A statistically significant and clinically meaningful improvement in
progression free survival (PFS) was observed for dostarlimab plus
carboplatin-paclitaxel in the mismatch repair deficient (dMMR)/microsatellite
instability-high (MSI-H) population (n=118) and in the overall population
(n=494) versus placebo plus chemotherapy. The separation of the lines in the
Kaplan-Meier curve below illustrates the significant reduction in risk of
disease progression or death in patients with dMMR/MSI-H primary advanced or
recurrent endometrial cancer in the dostarlimab plus chemotherapy treatment
arm compared to the placebo plus chemotherapy treatment arm.

Dr Mansoor Raza Mirza, Chief Oncologist, Copenhagen University Hospital,
Denmark and RUBY principal investigator, said: "Clinical practice has been
waiting decades for a meaningful advancement in the standard of care for
primary advanced or recurrent endometrial cancer. The results from the RUBY
clinical trial, especially given the difficult-to-treat histologies included
in the trial, demonstrate support for a new treatment standard with the
addition of dostarlimab to current standard-of-care chemotherapy."

 

Additionally, at this first interim analysis, there was a clinically
meaningful overall survival (OS) trend in the overall population among
patients receiving dostarlimab plus chemotherapy followed by dostarlimab. The
analysis was done at 33% maturity and statistical significance was not
reached. OS follow-up continues and further analysis is planned. PFS and OS
summaries are listed below.

 

                               dostarlimab + chemotherapy  placebo + chemotherapy
 PFS dMMR/MSI-H population
 Number of patients evaluated  53                          65
 HR (95% CI)                   0.28

                               (0.162-0.495)
 P-value                       P<0.0001
 At 24 months (95% CI)         61.4%                       15.7%

                               (46.3-73.4)                 (7.2-27.0)
 PFS overall patient population
 Number of patients evaluated  245                         249
 HR (95% CI)                   0.64

(0.507-0.800)
 P-value                       P<0.0001
 At 24 months (95% CI)         36.1%                       18.1%

                               (29.3%-42.9%)               (13.0%-23.9%)
 PFS mismatch repair proficient (MMRp)/microsatellite stable (MSS)
 population(a)
 Number of patients evaluated  192                         184
 HR (95% CI)                   0.76

(0.592-0.981)
 P-value                       N/A
 At 24 months (95% CI)         28.4%                       18.8%

                               (21.2-36.0)                 (12.8-25.7)
 OS overall patient population(b)
 HR (95% CI)                   0.64

(0.46-4-0.870)
 P-value                       P=0.0021(c)

 At 24 months (95% CI)         71.3%                       56.0%

(48.9-62.5)
                               (64.5-77.1)
 OS dMMR/MSI-H population(a,d)
 HR (95% CI)                   0.30

                               (0.127-0.699)
 P-value                       N/A
 At 24 months (95% CI)         83.3%                       58.7%

                               (66.8-92.0)                 (43.4-71.2)
 OS MMRp/MSS population(a,e)
 HR (95% CI)                   0.73

(0.515-1.024)
 P-value                       N/A
 At 24 months (95% CI)         67.7%                       55.1%

                               (59.8-74.4)                 (46.8-62.5)

(a)Exploratory analyses of PFS in MMRp/MSS, OS in dMMR/MSI-H, and OS in
MMRp/MSS populations were pre-specified with no planned hypothesis testing.
(b)Maturity ≈33%. (c)P-value of ≤0.00177 was required for statistical
significance at this OS interim analysis. (d)Maturity ≈26%. (e)Maturity
≈36%.

 

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. The most common
(>45%) treatment-emergent adverse events (TEAEs) in both treatment arms in
the dMMR/MSI-H and overall populations were nausea, alopecia and fatigue, as
well as anaemia in the placebo plus chemotherapy arm in the dMMR/MSI-H
population. Severe and serious TEAEs were approximately 10% higher in the
dostarlimab plus carboplatin-paclitaxel arm compared with the placebo plus
carboplatin-paclitaxel arm in the overall population. The nature and types of
immune-related adverse events (irAEs) in the dostarlimab plus chemotherapy
safety profile were consistent with the mechanism of action of dostarlimab and
similar to those reported for other PD-(L)1 inhibitors. In the overall
population, 38.2% of participants in the dostarlimab plus
carboplatin-paclitaxel arm and 15.4% of participants in the placebo plus
carboplatin-paclitaxel arm had irAEs assessed by the investigator as related
to dostarlimab or placebo, respectively. The most frequently reported
dostarlimab-related irAE categories were endocrinopathies (15.8%
dostarlimab-related versus 3.3% placebo-related) and skin adverse reactions
(14.1% dostarlimab-related versus 3.7% placebo-related). Discontinuation of
dostarlimab or placebo due to a TEAE occurred in 17.4% of patients in the
dostarlimab plus chemotherapy treatment arm and 9.3% of patients in the
placebo plus chemotherapy treatment arm in the overall population.

 

These data were shared in a European Society for Medical Oncology (ESMO)
Virtual Plenary, presented in a late breaking session at the Society of
Gynecologic Oncology (SGO) Annual Meeting on Women's Cancer (25-28 March) and
published simultaneously in The New England Journal of Medicine.

 

RUBY is part of an international collaboration between the European Network of
Gynaecological Oncological Trial groups (ENGOT), a research network of the
European Society of Gynaecological Oncology (ESGO) that consists of 22 trial
groups from 31 European countries that perform cooperative clinical trials;
the GOG Foundation, a non-profit organisation dedicated to transforming the
standard of care in gynaecologic oncology; and the Nordic Society of
Gynaecological Oncology - Clinical Trial Unit (NSGO-CTU), a non-profit
organisation aiming to improve the practice of prevention, diagnosis and
treatment for gynaecological cancers by supporting research and conducting
clinical trials across countries.

 

GSK's ambition is for dostarlimab to become the backbone of the Company's
ongoing immuno-oncology-based research and development programme when used
alone and in combination with standard of care and future novel cancer
therapies, particularly for patients who currently have limited treatment
options. Dostarlimab is being investigated in registrational enabling studies
as monotherapy and as part of combination regimens, including in patients with
primary advanced or recurrent endometrial cancer, patients with Stage III or
IV non-mucinous epithelial ovarian cancer, and patients with other advanced
solid tumours or metastatic cancers.

 

About endometrial cancer

Endometrial cancer is found in the inner lining of the uterus, known as the
endometrium. Endometrial cancer is the most common gynaecologic cancer in
developed countries, with approximately 417,000 new cases reported each year
worldwide([ i )(]), and incidence rates are expected to rise by almost 40% by
2040.([ ii ][ iii ]) Approximately 15-20% of patients with endometrial cancer
will be diagnosed with advanced disease at the time of diagnosis.([ iv ])

 

About RUBY

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.
Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by
dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed
by placebo. The primary endpoints in Part 1 are investigator-assessed PFS
based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS. The
statistical analysis plan included pre-specified analyses of PFS in the
dMMR/MSI-H and ITT populations and OS in the overall population. Pre-specified
exploratory analyses of PFS in the MMRp/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. In Part 2, the primary endpoint is investigator-assessed PFS.
Secondary endpoints in Part 1 and Part 2 include PFS per blinded independent
central review, overall response rate, duration of response, disease control
rate, patient-reported outcomes, and safety and tolerability.

 

About Jemperli (dostarlimab)

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds
to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1
and PD-L2.([ v ])

 

Jemperli is not approved anywhere in the world for use in combination with
standard-of-care chemotherapy (carboplatin-paclitaxel) followed by dostarlimab
for primary advanced or recurrent endometrial cancer. In the US, Jemperli is
indicated for adult patients with mismatch repair-deficient (dMMR) recurrent
or advanced endometrial cancer, as determined by a US FDA-approved test, that
has progressed on or following a prior platinum-containing regimen in any
setting and are not candidates for curative surgery or radiation. Jemperli is
also indicated in the US for patients with dMMR recurrent or advanced solid
tumours, as determined by a US FDA-approved test, that have progressed on or
following prior treatment and who have no satisfactory alternative treatment
options. The latter indication is approved in the US under accelerated
approval based on tumour response rate and durability of response. Continued
approval for this indication in solid tumours may be contingent upon
verification and description of clinical benefit in a confirmatory trial(s).

 

Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc.,
under a collaboration and exclusive license agreement signed in March 2014.
The collaboration has resulted in three monospecific antibody therapies that
have progressed into the clinic. These are: Jemperli (GSK4057190), a PD-1
antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a
LAG-3 antagonist. GSK is responsible for the ongoing research, development,
commercialisation, and manufacturing of each of these medicines under the
agreement.

 

Important Information for Jemperli in the EU

 

Indication 
Dostarlimab is indicated as monotherapy for the treatment of adult patients
with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H)
recurrent or advanced endometrial cancer that has progressed on or following
prior treatment with a platinum-containing regimen. 

 

Refer to the Jemperli
(https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli)
(https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli) EMA
(https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli) Reference
Information for a full list of adverse events and the complete important
safety information in the EU.

 

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/company
(https://www.gsk.com/en-gb/company/)

 

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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made
by GSK, including those made in this announcement, are subject to risks and
uncertainties that may cause actual results to differ materially from those
projected. Such factors include, but are not limited to, those described under
Item 3.D 'Risk factors" in the company's Annual Report on Form 20-F for 2022,
GSK's Q4 Results for 2022 and any impacts of the COVID-19 pandemic.

 

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References

 i  Faizan U, Muppidi V. Uterine Cancer. [Updated 2022 Sep 5]. In: StatPearls
 Internet . Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available
at: https://www.ncbi.nlm.nih.gov/books/NBK562313/.

 ii  Braun MM, et al. Am Fam Physician. 2016;93(6):468-474.

 iii  International Research on Cancer. Global Cancer Observatory. Cancer
Tomorrow. https://gco.iarc.fr/tomorrow/en/dataviz/. Accessed 13 July 2022.

 iv  Kantar Health, Cust Study (2018).

 v  Laken H, Kehry M, Mcneeley P, et al. Identification and characterization
of TSR-042, a novel anti-human PD-1 therapeutic antibody. European Journal of
Cancer. 2016;69,S102. doi:10.1016/s0959-8049(16)32902-1.

 

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