Issued: 16 March 2024, London
UK
Positive RUBY phase III data show potential for Jemperli (dostarlimab) combinations in
more patients with primary advanced or recurrent endometrial
cancer
· Dostarlimab plus chemotherapy is the
only immuno-oncology combination to show statistically significant
and clinically meaningful overall survival (OS) in the overall
population
· 31% reduction in risk of death
and 16.4-month improvement in median OS
observed with dostarlimab plus chemotherapy
versus chemotherapy in the overall
population
· 37% reduction in risk of disease progression or death and
6-month improvement in median progression-free survival observed
with the addition of Zejula (niraparib) to dostarlimab
maintenance following dostarlimab plus chemotherapy versus
chemotherapy in MMRp/MSS population where treatment options are
still needed
GSK plc (LSE/NYSE: GSK) today announced statistically significant
and clinically meaningful overall survival (OS) results from Part 1
and progression-free survival (PFS) results from Part 2 of the
RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial in adult patients with
primary advanced or recurrent endometrial cancer. These data were
presented today in a late-breaking plenary session at the Society
of Gynecologic Oncology 2024 Annual Meeting on Women's Cancer
(16-18 March).
The goal of the RUBY phase III trial
programme is to evaluate which patients with primary advanced or
recurrent endometrial cancer could potentially benefit from
treatment with Jemperli
(dostarlimab) plus chemotherapy, with or without the addition of
Zejula (niraparib)
maintenance. Part 1 of the RUBY phase III trial is
investigating dostarlimab plus standard-of-care chemotherapy
(carboplatin-paclitaxel) followed by dostarlimab compared to
chemotherapy plus placebo followed by placebo. Part 2 of the RUBY
phase III trial is evaluating dostarlimab plus standard-of-care
chemotherapy, followed by dostarlimab plus niraparib as maintenance
therapy compared to chemotherapy plus placebo followed by placebo.
The safety and tolerability profiles of dostarlimab plus
carboplatin-paclitaxel and dostarlimab plus carboplatin-paclitaxel
followed by dostarlimab plus niraparib were generally consistent
with the known safety profiles of the individual
medicines.
Previous data showed a statistically
significant and clinically meaningful improvement in PFS with
Jemperli plus chemotherapy
versus chemotherapy alone in frontline mismatch repair deficient
(dMMR)/microsatellite instability-high (MSI-H) primary advanced or
recurrent endometrial cancer. These data led to regulatory
approvals for this patient population in the US, EU and certain
other countries. Data presented today show additional potential
benefit of dostarlimab plus chemotherapy, with or without the
addition of niraparib, in the overall population of patients with
primary advanced or recurrent endometrial cancer, including
patients with mismatch repair proficient
(MMRp)/microsatellite stable (MSS) tumours, for which there are
currently no approved immuno-therapy-based regimens.
Hesham Abdullah, Senior Vice President, Global Head Oncology,
R&D, GSK said: "The positive data
presented today further show how dostarlimab-based regimens could
benefit a broader set of patients with endometrial cancer. The
results we've seen to date comprise the growing body of evidence
supporting the role of dostarlimab as the backbone of our
immuno-oncology development programme. Our goal is to continue to
identify ways to use dostarlimab alone and in combination with
other therapies to help improve outcomes for patients with limited
treatment options."
RUBY
Part 1: a statistically significant and clinically meaningful
improvement in OS was observed for dostarlimab plus chemotherapy
versus placebo plus chemotherapy, meeting a primary endpoint of the
study.
Dostarlimab plus chemotherapy versus
chemotherapy alone showed:
In the overall population:
· a
statistically significant reduction in the risk of death by 31%
(Hazard Ratio [HR]: 0.69; [95% CI: 0.539-0.890])
· a
clinically meaningful improvement of 16.4 months in median OS (44.6
months vs 28.2 months)
In a prespecified exploratory
analysis of the MMRp/MSS population:
· a
clinically meaningful trend in reduced risk of death by 21% (HR:
0.79; [95% CI: 0.602-1.044])
· a
clinically meaningful improvement of seven months in median OS
(34.0 months vs 27.0 months)
Full OS
summaries are shown below.
|
dostarlimab +
carboplatin-paclitaxel
|
placebo +
carboplatin-paclitaxel
|
Overall population, Number
(N)
|
245
|
249
|
OS, HR (95% CI)
|
0.69
(0.539-0.890)
|
P-value[1]
|
0.002
|
OS, median (95% CI), mo.
|
44.6
(32.6-NR)
|
28.2
(22.1-35.6)
|
dMMR/MSI-H
population2,
N
|
53
|
65
|
OS, HR (95% CI)
|
0.32
(0.166-0.629)
|
OS, median3 (95% CI), mo.
|
NR
(NR-NR)
|
31.4
(20.3-NR)
|
MMRp/MSS2, N
|
192
|
184
|
OS, HR (95% CI)
|
0.79
(0.602-1.044)
|
OS, median (95% CI), mo.
|
34.0
(28.6-NR)
|
27.0
(21.5-35.6)
|
|
1 One-sided
p-value based on stratified log-rank test.
2 Exploratory analyses of OS in
dMMR/MSI-H and OS in MMRp/MSS populations were pre-specified with
no planned hypothesis testing.
3 Although the median OS
was not reached, at 30 months the estimated reduction in the risk
of death was 82.8% for patients who received dostarlimab plus
chemotherapy vs. 54.1% for patients who received chemotherapy
alone.
Matthew Powell, MD, Division of Gynecologic Oncology,
Washington University School of
Medicine,
and US principal investigator
of the RUBY trial said:
"RUBY Part 1 is the first clinical trial to show a
statistically significant and clinically meaningful improvement in
overall survival for an immuno-oncology therapy in combination with
chemotherapy in the overall population of patients with primary
advanced or recurrent endometrial cancer. As a clinician, I celebrate the results of the RUBY Part 1
trial presented today, which show how dostarlimab added to
chemotherapy could potentially benefit a broader set of patients
with this type of cancer."
In RUBY Part 1, grade 3 or higher and
serious treatment-emergent adverse events (AEs) were approximately
12% higher in the dostarlimab plus carboplatin-paclitaxel arm
(treatment arm) compared with the placebo plus
carboplatin-paclitaxel arm (control arm). The nature and types of
immune-related AEs 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
trial, 40.7% of participants in the treatment arm and 16.3% of
participants in the control arm had immune-related AEs assessed by
the investigator as related to dostarlimab or placebo,
respectively. Discontinuation of dostarlimab or placebo due to a
treatment-emergent AE occurred in 19.1% of patients in the
treatment arm and 8.1% of patients in the control arm.
GSK expects US Food and Drug
Administration regulatory submission acceptance based on RUBY Part
1 data for an expanded indication in the overall population in the
first half of this year.
RUBY
Part 2: addition of niraparib to dostarlimab in maintenance setting
significantly improved PFS in first-line primary advanced or
recurrent endometrial cancer compared to chemotherapy alone,
meeting the primary endpoint of the trial.
Dostarlimab plus chemotherapy
followed by dostarlimab plus niraparib compared to placebo plus
chemotherapy followed by placebo showed:
In the overall population:
· a
statistically significant reduction in the risk of disease
progression or death by 40% (HR: 0.60 [95% CI:
0.43-0.82])
· a
clinically meaningful improvement of 6.2 months in median PFS (14.5
months vs 8.3 months)
In the MMRp/MSS
population:
· a
statistically significant reduction in the risk of disease
progression or death by 37% (HR: 0.63 [95% CI:
0.44-0.91])
· a
clinically meaningful improvement of 6.0 months in median PFS (14.3
months vs 8.3 months)
Dr
Mansoor Raza Mirza, Chief Oncologist, Copenhagen University
Hospital, Denmark, and RUBY principal investigator
said: "In RUBY Part 2, we observed
that the use of dostarlimab in combination with niraparib in the
maintenance therapy setting further improved progression-free
survival versus placebo for patients with primary advanced or
recurrent endometrial cancer. These findings are particularly
important for patients who have MMRp/MSS tumours as the data help
build on the initial benefit observed with an immuno-oncology plus
chemotherapy regimen, reflecting the potential for the addition of
niraparib maintenance to address unmet medical need for these
patients."
In RUBY Part 2, grade 3 or higher and
serious treatment-emergent AEs were approximately 36% and 24%
higher, respectively, in the dostarlimab plus chemotherapy followed
by dostarlimab plus niraparib arm (treatment arm) compared with the
placebo plus chemotherapy followed by placebo arm (control arm). In
the trial, 36.6% of participants in the treatment arm and 6.3% of
participants in the control arm had immune-related AEs assessed by
the investigator as related to dostarlimab or placebo,
respectively. No cases of myelodysplastic syndrome/acute myeloid
leukaemia were reported; other secondary primary malignancies
occurred in 1 patient each in both treatment arms. Discontinuation
of dostarlimab or placebo due to a TEAE occurred in 24.1% of
patients in the treatment arm and 5.2% of patients in the control
arm. Discontinuation of niraparib or placebo due to a
treatment-emergent AE occurred in 15.7% of patients in the
treatment arm and 4.2% of patients in the control arm.
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
worldwide1, and incidence rates
are expected to rise by almost 40% between 2020 and
2040.2,3 Approximately 15-20% of
patients with endometrial cancer will be diagnosed with advanced
disease at the time of diagnosis.4
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.
In Part 1, the dual-primary
endpoints 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 overall populations and OS in the
overall population. Pre-specified exploratory analyses of PFS and
OS 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 in the overall population, followed by
PFS in the MMRp/MSS population, and OS in the overall population is
a key secondary endpoint. Additional secondary endpoints in Part 1
and Part 2 include PFS per blinded independent central review,
PFS2, overall response rate, duration of response, disease control
rate, patient-reported outcomes, and safety and
tolerability.
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, and the GOG Foundation, a non-profit organisation
dedicated to transforming the standard of care in gynaecologic
oncology.
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-L2.5
In the US, Jemperli is indicated in combination
with carboplatin and paclitaxel, followed by Jemperli as a single agent for the
treatment of adult patients with primary advanced or recurrent
endometrial cancer that is dMMR, as determined by a US FDA-approved
test, or MSI-H, and as a single agent for adult patients with 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. The supplemental Biologics
License Application supporting the newly approved indication in
combination with carboplatin and paclitaxel for dMMR/MSI-H primary
advanced or recurrent endometrial cancer received Breakthrough
Therapy designation and Priority Review from the US FDA.
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. Under this agreement, GSK is responsible for the ongoing
research, development, commercialisation, and manufacturing of
Jemperli,
and cobolimab (GSK4069889), a TIM-3
antagonist.
Important Information for Jemperli in the
EU
Indication
Jemperli
is
indicated:
· in
combination with carboplatin-paclitaxel, 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
monotherapy for treating 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
(https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli)
for a full list of adverse events and the complete important
safety information in the EU.
About Zejula (niraparib)
Zejula is an
oral, once-daily poly(ADP-ribose) polymerase (PARP) inhibitor
indicated in the US for the maintenance treatment of adult patients
with advanced epithelial ovarian, fallopian tube, or primary
peritoneal cancer who are in complete or partial response to
first-line platinum-based chemotherapy; and for the maintenance treatment of adult patients with
deleterious or suspected deleterious germline BRCA-mutated recurrent epithelial
ovarian, fallopian tube, or primary peritoneal cancer who are in a
complete or partial response to platinum-based chemotherapy and who
have been selected based on a US FDA-approved companion diagnostic
for Zejula.
Important Information for
Zejula in the
EU
Indication
Zejula is
indicated:
· as
monotherapy for the maintenance treatment of adult patients with
advanced epithelial (FIGO Stages III and IV) high-grade ovarian,
fallopian tube or primary peritoneal cancer who are in response
(complete or partial) following completion of first-line
platinum-based chemotherapy.
· as
monotherapy for the maintenance treatment of adult patients with
platinum-sensitive relapsed high-grade serous epithelial ovarian,
fallopian tube, or primary peritoneal cancer who are in response
(complete or partial) to platinum-based
chemotherapy.
Refer to the Zejula EMA Reference Information
(https://www.ema.europa.eu/en/medicines/human/EPAR/zejula)
for a full list of adverse events and the complete
important safety information in the EU.
GSK in oncology
Oncology is an emerging therapeutic
area for GSK where we are committed to maximising patient survival
with a current focus on haematologic malignancies, gynaecologic
cancers and other solid tumours through breakthroughs in
immuno-oncology and tumour-cell targeting therapies.
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.
GSK
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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
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limited to, those described under Item 3.D "Risk factors" in the
company's Annual Report on Form 20-F for 2023.
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References
1. Faizan U,
Muppidi V. Uterine Cancer. [Updated 2022 Sep 5]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
Available at: www.ncbi.nlm.nih.gov/books/NBK562313/.
2.
Braun MM, et al. Am Fam Physician.
2016;93(6):468-474.
3.
International Research on Cancer. Global Cancer Observatory. Cancer
Tomorrow. gco.iarc.fr/tomorrow/en/dataviz/. Accessed 13 July
2022.
4.
CMP: CancerMPact® Patient Metrics Mar-2023, Cerner
Enviza. Available at www.cancermpact.com.
Accessed 29 Feb 2024.
5. 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.