TIDMGSK
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%
(64.5-77.1) (48.9-62.5)
--------------------------- -----------------------
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 .APPROX.33%. (c) P-value of
<=0.00177 was required for statistical significance at this OS
interim analysis. (d) Maturity .APPROX.26%. (e) Maturity
.APPROX.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 EMA 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
GSK enquiries
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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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