a2253h
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Form 6-K
REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a-16 OR
15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
For the
month of March 2024
Commission
File Number 001-15170
GSK plc
(Translation
of registrant's name into English)
980 Great West Road, Brentford, Middlesex, TW8 9GS
(Address
of principal executive office)
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F . . . .X. . . . Form 40-F . . . . . . . .
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 enquiries
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Media:
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Tim
Foley
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+44 (0)
20 8047 5502
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(London)
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Dan
Smith
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+44 (0)
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(London)
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Kathleen
Quinn
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+1 202
603 5003
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(Washington
DC)
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Lyndsay
Meyer
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+1 202
302 4595
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(Washington
DC)
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Investor
Relations:
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Nick
Stone
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+44 (0)
7717 618834
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(London)
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James
Dodwell
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+44 (0)
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Mick
Readey
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+44 (0)
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Josh
Williams
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+44 (0)
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(London)
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Camilla
Campbell
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+44 (0)
7803 050238
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(London)
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Steph
Mountifield
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+44 (0)
7796 707505
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(London)
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Jeff
McLaughlin
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+1 215
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(Philadelphia)
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Frannie
DeFranco
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+1 215
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(Philadelphia)
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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
2023.
Registered in England & Wales:
No.
3888792
Registered Office:
980
Great West Road
Brentford,
Middlesex
TW8
9GS
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.
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorised.
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GSK plc
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(Registrant)
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Date: March
18, 2024
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By:/s/ VICTORIA
WHYTE
--------------------------
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Victoria Whyte
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Authorised
Signatory for and on
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behalf
of GSK plc
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