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 April 2021
Commission
File Number 001-15170
GlaxoSmithKline plc
(Translation
of registrant's name into English)
980 Great West Road, Brentford, Middlesex, TW8 9GS
(Address
of principal executive office)
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Issued: 23 April 2021, London UK
European Commission
approves GSK's JEMPERLI (dostarlimab), the first anti-PD-1 therapy
approved for recurrent or advanced
endometrial cancer
GlaxoSmithKline (LSE/NYSE: GSK) plc today announced the European
Commission has granted conditional marketing authorisation for
JEMPERLI (dostarlimab), a programmed death receptor-1
(PD-1)-blocking antibody, for use in women with
mismatch repair-deficient (dMMR)/microsatellite instability-high
(MSI-H) recurrent or advanced endometrial cancer who have
progressed on or following prior treatment with a platinum
containing regimen. The approval makes dostarlimab the first
anti-PD-1 therapy available for endometrial cancer in
Europe.
Dr Hal Barron, Chief Scientific Officer and President R&D, GSK,
said: "Women with
recurrent endometrial cancer, or advanced disease that
has progressed on or after chemotherapy, currently have limited treatment options and
a poor prognosis. Today's approval of dostarlimab means
that for the first time in Europe, these women will have access to
a new, innovative and much-needed therapy."
Dr Ana Oaknin, Head of the Gynaecologic Cancer Program at Vall
d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University
Hospital, Barcelona, Spain, and primary investigator for the GARNET
Trial, said: "As we saw in the pivotal GARNET trial
that supported this approval, treatment with dostarlimab has the potential to
provide clinically significant and durable responses in patients
who formerly had few treatment options. This approval represents a
step forward, providing a new treatment for women with recurrent or
advanced dMMR/MSI-H endometrial cancer who have previously failed a
platinum-based chemotherapy."
Icó Tóth, Co-Chair of European Network of
Gynaecological Cancer Advocacy Groups (ENGAGe), Council member for
European Society of Gynaecological Oncology (ESGO), President,
Mallow Flower Foundation, Hungary, said: "Today's approval of
dostarlimab offers a new treatment option for
women with recurrent or advanced dMMR/MSI-H endometrial cancer.
We're inspired by the efforts of companies like GSK who are
continuing to innovate for patients in dire need of new
options."
Endometrial cancer is found in the inner lining of the uterus,
known as the endometrium. It is the most common type of cancer that
affects the female reproductive organs and is the sixth most
prevalent cancer in women worldwide.[i] Endometrial
cancer has the highest rate of the MSI-H phenotype of all
tumours.[ii]
The
European Medicine Agency's approval of dostarlimab is based on results from
the multi-cohort GARNET study, which included women with recurrent
or advanced dMMR/MSI-H endometrial cancer who progressed on or
after a platinum-based chemotherapy regimen in cohort A1 (n=108
evaluable for efficacy). Treatment with dostarlimab resulted in an
objective response rate (ORR) of 43.5% (95% CI; 34-53.4) and a
disease control rate of 55.6% (95% CI; 45.7-65.1). The median
duration of response (DoR) had not been reached (2.6 to 28.1+
months) in these patients, and the probability of maintaining a
response at six months and 12 months was 97.9% (95% CI; 85.8, 99.7)
and 90.9% (95% CI; 73.7, 97.1), respectively.
In the
515 patients with advanced or recurrent solid tumours who
participated in the GARNET study, including 129 patients evaluable
for safety from cohort A1, the most common adverse reactions
(occurring in more than 10% of patients) were anaemia (25.6%),
nausea (25.0%), diarrhoea (22.5%), vomiting (18.4
%), arthralgia
(13.8 %), pruritus (11.5%), rash (11.1%), pyrexia
(10.5%) and hypothyroidism (10.1%). Dostarlimab was permanently
discontinued due to adverse reactions in 17 patients (3.3%); most
were immune-related events. Serious adverse reactions occurred in
8.7% of patients; most were immune-related adverse
reactions. The safety profile for
patients in cohort A1 was comparable with the overall study
population.
GSK is also studying dostarlimab for endometrial cancer in earlier
treatment lines and in combination with other therapeutic agents
for patients with advanced solid tumours or metastatic cancer as we
work to expand our oncology pipeline and reinforce our
portfolio of cancer treatments.
###
About GARNET
The ongoing phase 1 GARNET trial is
evaluating dostarlimab as monotherapy in patients with
advanced solid tumours. Part 2B of the study includes five
expansion cohorts: dMMR/MSI-H endometrial cancer (cohort A1),
mismatch repair proficient/microsatellite stable (MMRp/MSS)
endometrial cancer (cohort A2), non-small cell lung cancer (cohort
E), dMMR/MSI-H non-endometrial or POLE-mut solid tumour basket
cohort (cohort F), and platinum-resistant ovarian cancer
without BRCA mutations
(cohort G). GARNET is ongoing and enrolling patients in certain
cohorts.
About JEMPERLI (dostarlimab)
Dostarlimab is a programmed death receptor-1 (PD-1)-blocking
antibody that binds with high affinity to the PD-1 receptor and
blocks its interaction with the ligands PD-L1 and
PD-L2.[iii] In
addition to GARNET, dostarlimab is being investigated in other
registrational-enabling studies, as monotherapy and as part of
combination regimens for women with recurrent or primary advanced
endometrial cancer stage III or IV non-mucinous epithelial ovarian
cancer for patients with advanced solid tumours or metastatic
cancer.
Dostarlimab was discovered by AnaptysBio and
licensed to TESARO, Inc., under a Collaboration and Exclusive
License Agreement signed in March 2014. The collaboration has
resulted in three monospecific antibody drugs that have progressed
into the clinic. These are: dostarlimab (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 manufacture of each
of these products under the Agreement.
Important Information for JEMPERLI in the EU
Indication
JEMPERLI 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 (EC) that has progressed on or
following prior treatment with a platinum-containing
regimen.
Immune-Mediated Adverse Reactions
Immune-related adverse reactions, which may be severe or fatal, can
occur in patients treated with antibodies blocking the programmed
cell death protein-1 / programmed death-ligand 1 (PD-1/PD-L1)
pathway, including JEMPERLI. While immune-related adverse
reactions usually occur during treatment with PD-1/PD-L1 blocking
antibodies, symptoms can also manifest after discontinuation of
treatment. Immune-related adverse reactions may occur in any organ
or tissue and may affect more than one body system simultaneously.
Important immune-related adverse reactions listed in this section
are not inclusive of all possible severe and fatal immune-related
reactions.
Early identification and management of immune-related adverse
reactions are essential to ensure safe use of PD-1/PD-L1 blocking
antibodies. Patients should be monitored for symptoms and signs of
immune-related adverse reactions. Clinical chemistries, including
liver tests and thyroid function tests, should be evaluated at
baseline and periodically during treatment. For suspected
immune-related adverse reactions, adequate evaluation including
specialty consultation should be ensured.
Based on the severity of the adverse reaction, treatment
with JEMPERLI should be withheld or permanently
discontinued and corticosteroids (1 to 2 mg/kg/day prednisone
or equivalent) or other appropriate therapy administered. Upon
improvement to Grade ≤1, corticosteroid taper should be
initiated and continued for 1 month or longer. Based on
limited data from clinical studies in patients whose immune-related
adverse reactions could not be controlled with corticosteroid use,
administration of other systemic immunosuppressants can be
considered. Hormone replacement therapy for endocrinopathies should
be instituted as warranted.
Treatment with JEMPERLI should be permanently
discontinued for any Grade 3 immune-related adverse reaction
that recurs and for any Grade 4 immune-related adverse
reaction toxicity, except for endocrinopathies that are controlled
with replacement hormones and unless otherwise specified in the
Summary of Product Characteristics (SmPC).
Immune-Related Pneumonitis
Pneumonitis has been reported in patients receiving JEMPERLI.
Patients should be monitored for signs and symptoms of pneumonitis.
Suspected pneumonitis should be confirmed with radiographic imaging
and other causes excluded. Patients should be managed with
JEMPERLI treatment modifications and
corticosteroids.
Immune-related pneumonitis occurred in 7 (1.4%) of
515 patients, including Grade 2 (1.2%) and Grade 3
(0.2%) pneumonitis. Pneumonitis led to discontinuation of
JEMPERLI in 3 (0.6%) patients. Systemic
corticosteroids (prednisone ≥ 40 mg per day or equivalent)
were required in all 7 patients experiencing pneumonitis.
Pneumonitis resolved in 6 (85.7%) patients.
Immune-Related Colitis
JEMPERLI can cause immune-related colitis.
Patients should be monitored for signs and symptoms of colitis and
managed with treatment modifications, anti-diarrhoeal agents and
corticosteroids.
Colitis occurred in 8 (1.6%) patients, including Grade 2
(1.0%) and Grade 3 (0.6%) colitis. Colitis did not lead to
discontinuation of JEMPERLI in any patients. Systemic
corticosteroids (prednisone ≥ 40 mg per day or
equivalent) were required in 2 (28.6%) patients. Colitis resolved
in 6 (75.0%) patients experiencing colitis.
Immune-Related Hepatitis
JEMPERLI can cause immune-related
hepatitis. Patients should be monitored for changes in liver
function periodically as indicated, based on clinical evaluation
and managed with JEMPERLI treatment modifications and
corticosteroids.
Hepatitis occurred in 1 (0.2%) patient, which was Grade 3.
Systemic corticosteroids (prednisone ≥ 40 mg per
day or equivalent) were required. Hepatitis did not lead to
discontinuation of JEMPERLI and resolved.
Immune-Mediated Endocrinopathies
Hypothyroidism occurred in 37 (7.2%) patients, all of which were
Grade 2. Hypothyroidism did not lead to discontinuation
of JEMPERLI and resolved in 13 (35.1%)
patients.
Hyperthyroidism occurred in 10 (1.9%) patients, including
Grade 2 (1.7%) and Grade 3 (0.2%). Hyperthyroidism did
not lead to discontinuation of JEMPERLI and resolved in 8 (80%)
patients.
Thyroiditis occurred in 2 (0.4%) patients; both were Grade 2.
Neither event of thyroiditis resolved; there were no
discontinuations of JEMPERLI due to
thyroiditis.
Adrenal insufficiency occurred in 7 (1.4%) patients, including
Grade 2 (0.8%), and Grade 3 (0.6%). Adrenal insufficiency
resulted in discontinuation of JEMPERLI in 1 (0.2%) patient and resolved
in 2 (28.6%) patients.
Immune-Mediated Nephritis
Nephritis, including tubulointerstitial nephritis, occurred in 3
(0.6%) patients; all were Grade 2. Systemic corticosteroids
(prednisone ≥ 40 mg per day or equivalent) were
required in 2 (66.7%) patients experiencing nephritis. Nephritis
led to discontinuation of JEMPERLI in 1 (0.2%) patient and resolved
in 2 of 3 (66.7%) patients.
Immune-Related Rash
Immune-related rash occurred in 17 (3.3%) patients, including
Grade 3 in 6 (1.2%) patients receiving JEMPERLI. The median
time to onset of rash was 41 days (range 2 days to
407 days). Systemic corticosteroids (prednisone
≥ 40 mg per day or equivalent) were required in 5
(29%) patients experiencing rash. Rash did not lead to
discontinuation of JEMPERLI and resolved in 13 (76.5%)
patients.
Immune-Related Arthralgia
Immune-related arthralgia occurred in 21 (4.1%) patients.
Grade 3 immune-related arthralgia was reported in 3 (0.6%)
patients receiving JEMPERLI. The median time to onset of arthralgia
was 87 days (range 1 day to 783 days). Systemic
corticosteroids (prednisone ≥ 40 mg per day or
equivalent) were required in 2 (9.5%) patients experiencing
arthralgia. Arthralgia did not lead to discontinuation of
JEMPERLI and resolved in 8 (38%) patients
experiencing arthralgia.
Other Immune-Related Adverse Reactions
Given the mechanism of action of JEMPERLI other potential immune-related
adverse reactions may occur, including potentially serious events
[e.g. myositis, myocarditis, encephalitis, demyelinating neuropathy
(including Guillain Barré syndrome),
sarcoidosis].
Clinically significant immune-related adverse reactions reported in
less than 1% of patients treated with JEMPERLI as monotherapy in clinical
studies include autoimmune haemolytic anaemia, pancreatitis,
iridocyclitis, uveitis and diabetic ketoacidosis. Patients should
be monitored for signs and symptoms of immune-related adverse
reactions and managed as described in the SmPC.
Solid organ transplant rejection has been reported in the
post-marketing setting in patients treated with PD-1 inhibitors.
Treatment with JEMPERLI may increase the risk of
rejection in solid organ transplant recipients. The benefit of
treatment with JEMPERLI versus the risk of possible organ
rejection should be considered in these
patients.
Fatal and other serious complications can occur in patients who
receive allogeneic haematopoietic stem cell transplantation (HSCT)
before or after being treated with a PD-1/PD-L1-blocking antibody.
Transplant-related complications include hyperacute
graft-versus-host disease (GvHD), acute GvHD, chronic GvHD, hepatic
veno-occlusive disease after reduced intensity conditioning, and
steroid-requiring febrile syndrome (without an identified
infectious cause). These complications may occur despite
intervening therapy between PD-1/PD-L1 blockade and allogeneic
HSCT. Follow patients closely for evidence of transplant-related
complications and intervene promptly. Consider the benefit versus
risks of treatment with a PD-1/PD-L1-blocking antibody prior to or
after an allogeneic HSCT.
Infusion-Related Reactions
Infusion-related reactions including hypersensitivity occurred in 7
(1.4%) patients, including Grade 2 (1.2%) and Grade 3
(0.2%) infusion-related reactions. All patients recovered from the
infusion-related reaction.
Immunogenicity
Anti-drug antibodies (ADA) were tested in 315 patients who
received JEMPERLI and the incidence of
JEMPERLI treatment-emergent ADAs was 2.5%.
Neutralising antibodies were detected in 1.3% of patients. In the
patients who developed anti-JEMPERLI antibodies, there was no
evidence of altered efficacy or safety of
JEMPERLI.
Elderly population
Of the 515 patients treated with JEMPERLI
monotherapy, 50.7% were under 65 years, 37.9% were
65-75 years, and 11.5% were 75 years or
older. No overall differences in safety were reported between
elderly (≥ 65 years) and younger patients
(< 65 years).
Pregnancy, Lactation and Fertility
JEMPERLI is not recommended during pregnancy and in women of
childbearing potential not using contraception.
JEMPERLI should not be used during
breast-feeding and breast-feeding should be
avoided for at least 4 months after the last dose of
JEMPERLI. Fertility studies have not been conducted with
JEMPERLI.
COMMON ADVERSE REACTIONS
JEMPERLI is most commonly associated with immune-related
adverse reactions. Most of these, including severe reactions,
resolved following initiation of appropriate medical therapy or
withdrawal of JEMPERLI.
In patients with advanced or recurrent solid tumours
(N = 515), the most common adverse reactions
(> 10%) were anaemia (25.6%), nausea (25.0%), diarrhoea
(22.5%), vomiting (18.4%), arthralgia (13.8%),
pruritus (11.5%), rash (11.1%), pyrexia (10.5%) and
hypothyroidism (10.1%). JEMPERLI was permanently discontinued
due to adverse reactions in 17 (3.3%) patients; most of them were
immune-related events. Adverse reactions were serious in 8.7% of
patients; most serious adverse reactions were immune-related
adverse reactions.
Refer to the JEMPERLI Prescribing Information for a full
list of adverse events and the complete important safety
information.
GSK in Oncology
GSK is focused on maximising patient survival through
transformational medicines. GSK's pipeline is focused on
immuno-oncology, cell therapy, cancer epigenetics 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,
antibody drug conjugates and cells, either alone or in
combination.
About GSK
GSK is a science-led global healthcare company with a special
purpose: to help people do more, feel better, live longer. For
further information please visit www.gsk.com/about-us.
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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
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pandemic.
Registered in England & Wales:
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9GS
[i] Endometrial cancer
statistics. World Cancer Research Fund. https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data.
Published 2018. Accessed January 2021.
[ii] Bonneville R, Krook
MA, Kautto EA, et al. Landscape of Microsatellite Instability
Across 39 Cancer Types. JCO Precis
Oncol.
2017;1-15.
[iii] 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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GlaxoSmithKline plc
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(Registrant)
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Date: April
23, 2021
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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 GlaxoSmithKline plc
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