TIDMGSK
RNS Number : 3740W
GlaxoSmithKline PLC
22 April 2021
Issued: 22 April 2021, London UK - LSE announcement
FDA grants accelerated approval for GSK's JEMPERLI
(dostarlimab-gxly) for women with recurrent or advanced dMMR
endometrial cancer
-- GARNET study represents the largest dataset of anti-PD-1
monotherapy treatment of women with endometrial cancer
-- Study results showed an overall response rate of 42%
-- 93% of responders had a duration of response of >=6 months
GlaxoSmithKline plc (LSE/NYSE: GSK) today announced that the US
Food and Drug Administration (FDA) has approved JEMPERLI
(dostarlimab-gxly), a programmed death receptor-1 (PD-1) blocking
antibody, based on the company's Biologics License Application.
Dostarlimab is indicated for the treatment of adult patients with
mismatch repair-deficient (dMMR) recurrent or advanced endometrial
cancer, as determined by an FDA-approved test, that have progressed
on or following prior treatment with a platinum-containing regimen.
This indication is approved under accelerated approval based on
tumour response rate and durability of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in a confirmatory trial(s).
Dr Hal Barron, Chief Scientific Officer and President R&D,
GSK, said: "Unfortunately, as many as 60,000 women are diagnosed
with endometrial cancer in the US each year and these women
currently have limited treatment options if their disease
progresses on or after first-line therapy. Today's approval of
dostarlimab by the FDA has the potential to transform the treatment
landscape for these women and demonstrates our continued commitment
to helping patients with gynaecologic cancers."
Around 1 in 4 women with endometrial cancer may experience a
recurrence or be diagnosed with advanced disease. [i](, [ii]) For
women whose disease recurs after platinum-based chemotherapy, there
is generally no accepted standard of care. [iii] , [iv](, [v])
Additionally, endometrial cancer has the highest rate of dMMR among
tumour types [vi](, [vii]) at approximately 25%, (vii) and
increased rates of recurrence have been reported for women with
dMMR endometrial cancer. [viii]
Dr Jubilee Brown, Professor and Division Director of
Gynaecologic Oncology at Levine Cancer Institute, Atrium Health,
and investigator on the GARNET study, noted: "The approval of
dostarlimab has the potential to change the way we've been treating
dMMR advanced or recurrent endometrial cancer after standard
platinum-based chemotherapy, especially given the overall response
rate and durability of response that we saw in the GARNET
trial."
The approval is based on results from the dMMR endometrial
cancer cohort of the ongoing GARNET trial, a large, multicentre,
non-randomised, multiple parallel-cohort, open-label study,
representing the largest dataset to date evaluating an anti-PD-1
antibody as monotherapy treatment in women with endometrial cancer.
(v) The approval was granted under the FDA's Real-Time Oncology
Review pilot programme, and dostarlimab was initially granted
breakthrough therapy designation in May of 2019 for recurrent or
advanced dMMR endometrial cancer.
The primary endpoints in the GARNET trial were overall response
rate (ORR) and duration of response (DOR) as assessed by blinded
independent central review (BICR). Results showed an ORR of 42.3%
(95% CI; 30.6-54.6) with a complete response (CR) rate of 12.7% and
partial response rate (PR) of 29.6% among the 71 evaluable patients
with dMMR advanced or recurrent endometrial cancer who had
progressed on or after treatment with a platinum-containing
regimen. Of those that responded, 93.3% demonstrated a DOR of 6
months or more. After a median follow-up of 14.1 months, the median
duration of response was not reached (2.6-22.4+).
Patients received 500 mg of dostarlimab as an intravenous
infusion once every three weeks for four doses, followed by 1,000
mg once every six weeks until disease progression or unacceptable
toxicity. Among the 104 patients evaluable for safety, the most
commonly reported adverse reactions (occurring in 20% or more of
patients) were fatigue/asthenia (48%), nausea (30%), diarrhoea
(26%), anaemia (24%) and constipation (20%). The most common Grade
3 or 4 adverse reactions (>=2%) were anaemia and transaminases
increase. Dostarlimab was permanently discontinued due to adverse
reactions in 5 (4.8%) patients. No deaths attributed to dostarlimab
were reported in the study.
Dr Sue Friedman, Executive Director of Facing Our Risk of Cancer
Empowered (FORCE), commented: "We applaud GSK and their ongoing
efforts to support women with endometrial cancer, the most common
gynaecologic malignancy in the US and the sixth most common cancer
in women worldwide. For many women whose disease is dMMR and has
progressed after platinum-based chemotherapy, the approval of
dostarlimab brings a new treatment option to an underserved patient
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 Endometrial Cancer
Endometrial cancer is a main type of uterine cancer that forms
in the inner lining of the uterus, known as the endometrium. [ix]
Endometrial cancer can be classified as mismatch
repair-deficient/microsatellite instability-high (dMMR/MSI-H) or
mismatch repair-proficient/microsatellite stable. There are limited
treatment options for women whose disease progresses on or after
first-line thera py. (ix) N early 60,000 new cases of endometrial
cancer are expected in the US in 2021, making endometrial cancer
the most common gynaecologic malignancy in the US. [x](, [xi])
Approximately 25% of women with endometrial cancer will be
diagnosed with advanced disease or will experience a recurrence.
(i) (,) (ii)
About GARNET
The ongoing phase I 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 still
enrolling patients.
About JEMPERLI (dostarlimab-gxly)
Dostarlimab 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. (xiii) 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 therapies 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, commercialization, and manufacture of each of these
Products under the Agreement.
Important Safety Information for JEMPERLI
Indication
-- JEMPERLI is indicated for the treatment of adult patients
with mismatch repair deficient (dMMR) recurrent or advanced
endometrial cancer (EC), as determined by an FDA-approved test,
that has progressed on or following prior treatment with a
platinum-containing regimen.
-- This indication is approved under accelerated approval based
on tumour response rate and durability of response. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in a confirmatory trial(s).
Important Safety Information
Immune-Mediated Adverse Reactions
-- Immune-mediated adverse reactions, which can be severe or
fatal, can occur in any organ system or tissue and can occur at any
time during or after treatment with a PD-1/PD-L1-blocking antibody,
including JEMPERLI.
-- Monitor closely for signs and symptoms of immune-mediated
adverse reactions. Evaluate liver enzymes, creatinine, and thyroid
function tests at baseline and periodically during treatment. For
suspected immune-mediated adverse reactions, initiate appropriate
workup to exclude alternative etiologies, including infection.
Institute medical management promptly, including specialty
consultation as appropriate.
-- Based on the severity of the adverse reaction, withhold or
permanently discontinue JEMPERLI. In general, if JEMPERLI requires
interruption or discontinuation, administer systemic
corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) until
improvement to <=Grade 1. Upon improvement to <=Grade 1,
initiate corticosteroid taper and continue to taper over at least 1
month. Consider administration of other systemic immunosuppressants
in patients whose immune-mediated adverse reaction is not
controlled with corticosteroids.
Immune-Mediated Pneumonitis
-- JEMPERLI can cause immune-mediated pneumonitis, which can be
fatal. The incidence of pneumonitis in patients receiving
PD-1/PD-L1 inhibitors, including JEMPERLI, may be increased in
patients who have received prior thoracic radiation.
-- Immune-mediated pneumonitis occurred in 1.1% (5/444) of
patients, including Grade 2 (0.9%) and Grade 3 (0.2%) pneumonitis.
Pneumonitis led to discontinuation of JEMPERLI in 0.7% of patients.
Systemic corticosteroids were required in all patients with
pneumonitis. Pneumonitis resolved in 80% of the 5 patients. Three
patients reinitiated JEMPERLI after symptom improvement; of these,
33% had recurrence of pneumonitis.
Immune-Mediated Colitis
-- JEMPERLI can cause immune-mediated colitis. Cytomegalovirus
infection/reactivation have occurred in patients with
corticosteroid-refractory immune-mediated colitis treated with
PD-1/PD-L1-blocking antibodies. In cases of
corticosteroid-refractory colitis, consider repeating infectious
workup to exclude alternative etiologies.
-- Immune-mediated colitis occurred in 1.4% (6/444) of patients,
including Grade 3 (0.7%) and Grade 2 (0.7%). Colitis did not lead
to discontinuation of JEMPERLI in any patients. Systemic
corticosteroids were required in 17% (1/6) of patients with
colitis. Colitis resolved in 50% of the 6 patients. Of the 2
patients in whom JEMPERLI was withheld for colitis, both
reinitiated JEMPERLI.
Immune-Mediated Hepatitis
-- JEMPERLI can cause immune-mediated hepatitis, which can be
fatal. Immune-mediated Grade 3 hepatitis occurred in 0.2% (1/444)
of patients. Systemic corticosteroids were required, and the event
resolved.
Immune-Mediated Endocrinopathies
-- Adrenal Insufficiency
o JEMPERLI can cause primary or secondary adrenal insufficiency.
For Grade 2 or higher adrenal insufficiency, initiate symptomatic
treatment per institutional guidelines, including hormone
replacement as clinically indicated. Withhold JEMPERLI if not
clinically stable. Adrenal insufficiency occurred in 0.9% (4/444)
of patients, including Grade 3 (0.5%) and Grade 2 (0.5%). Adrenal
insufficiency resulted in discontinuation in 1 (0.2%) patient and
resolved in 25% of the 4 patients.
-- Hypophysitis
o JEMPERLI can cause immune-mediated hypophysitis. Hypophysitis
can present with acute symptoms associated with mass effect such as
headache, photophobia, or visual field cuts. Hypophysitis can cause
hypopituitarism. Initiate hormone replacement as clinically
indicated. Withhold JEMPERLI if not clinically stable.
-- Thyroid Disorders
o JEMPERLI can cause immune-mediated thyroid disorders.
Thyroiditis can present with or without endocrinopathy.
Hypothyroidism can follow hyperthyroidism. Initiate hormone
replacement or medical management of hyperthyroidism as clinically
indicated. Withhold JEMPERLI if not clinically stable.
o Thyroiditis occurred in 0.5% (2/444) of patients; both were
Grade 2. Neither event of thyroiditis resolved; there were no
discontinuations of JEMPERLI due to thyroiditis.
o Hypothyroidism occurred in 5.6% (25/444) of patients, all of
which were Grade 2. Hypothyroidism did not lead to discontinuation
of JEMPERLI and resolved in 40% of the 25 patients. Systemic
corticosteroids were not required for any of the 25 patients with
hypothyroidism.
o Hyperthyroidism occurred in 1.8% (8/444) of patients,
including Grade 2 (1.6%) and Grade 3 (0.2%). Hyperthyroidism did
not lead to discontinuation of JEMPERLI and resolved in 63% of the
8 patients. Systemic corticosteroids were not required for any of
the 8 patients with hyperthyroidism.
-- Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis
o JEMPERLI can cause type 1 diabetes mellitus, which can present
with diabetic ketoacidosis. Monitor patients for hyperglycemia or
other signs and symptoms of diabetes. Initiate treatment with
insulin as clinically indicated. Withhold or permanently
discontinue JEMPERLI depending on severity.
Immune-Mediated Nephritis with Renal Dysfunction
-- JEMPERLI can cause immune-mediated nephritis, which can be
fatal. Nephritis occurred in 0.5% (2/444) of patients; both were
Grade 2. Nephritis did not lead to discontinuation of JEMPERLI and
resolved in both patients. Systemic corticosteroids were required
in 1 of the 2 patients experiencing nephritis.
Immune-Mediated Dermatologic Adverse Reactions
-- JEMPERLI can cause immune-mediated rash or dermatitis.
Bullous and exfoliative dermatitis, including Stevens-Johnson
syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash
with eosinophilia and systemic symptoms (DRESS), have occurred with
PD-1/PD-L1-blocking antibodies. Topical emollients and/or topical
corticosteroids may be adequate to treat mild to moderate
non-bullous/exfoliative rashes. Withhold or permanently discontinue
JEMPERLI depending on severity.
Other Immune-Mediated Adverse Reactions
-- The following clinically significant immune-mediated adverse
reactions occurred in <1% of the 444 patients treated with
JEMPERLI or were reported with the use of other PD-1/PD-L1-blocking
antibodies. Severe or fatal cases have been reported for some of
these adverse reactions.
o Nervous System: Meningitis, encephalitis, myelitis and
demyelination, myasthenic syndrome/myasthenia gravis,
Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy
o Cardiac/Vascular: Myocarditis, pericarditis, vasculitis
o Ocular: Uveitis, iritis, other ocular inflammatory toxicities.
Some cases can be associated with retinal detachment. Various
grades of visual impairment to include blindness can occur.
o Gastrointestinal: Pancreatitis, including increases in serum
amylase and lipase levels, gastritis, duodenitis
o Musculoskeletal and Connective Tissue: Myositis/polymyositis,
rhabdomyolysis and associated sequelae including renal failure,
arthritis, polymyalgia rheumatica
o Endocrine: Hypoparathyroidism
o Other (Hematologic/Immune): Haemolytic anaemia, aplastic
anaemia, hemophagocytic lymphohistiocytosis, systemic inflammatory
response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ
transplant rejection
Infusion-Related Reactions
-- Severe or life-threatening infusion-related reactions have
been reported with PD-1/PD-L1-blocking antibodies. Severe
infusion-related reactions (Grade 3) occurred in 0.2% (1/444) of
patients receiving JEMPERLI. All patients recovered from the
infusion-related reactions.
-- Monitor patients for signs and symptoms of infusion-related
reactions. Interrupt or slow the rate of infusion or permanently
discontinue JEMPERLI based on severity of reaction.
Complications of Allogeneic HSCT after PD-1/PD-L1-Blocking
Antibody:
-- Fatal and other serious complications can occur in patients
who receive allogeneic hematopoietic stem cell transplantation
(HSCT) before or after treatment with a PD-1/PD-L1-blocking
antibody. 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.
Embryo-Fetal Toxicity and Lactation:
-- Based on its mechanism of action, JEMPERLI can cause fetal
harm. Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective
contraception during treatment with JEMPERLI and for 4 months after
their last dose. Because of the potential for serious adverse
reactions from JEMPERLI in a breastfed child, advise women not to
breastfeed during treatment with JEMPERLI and for 4 months after
their last dose.
Common Adverse Reactions
-- The most common adverse reactions (Grades 1-4) in >=10% of
104 dMMR endometrial cancer patients who received JEMPERLI as
monotherapy were fatigue (48%), nausea (30%), diarrhoea (26%),
anaemia (24%), constipation (20%), vomiting (18%), pruritus (14%),
cough (14%), decreased appetite (14%), urinary tract infection
(13%), and myalgia (12%).
-- JEMPERLI was permanently discontinued due to adverse
reactions in 5 (4.8%) patients, including transaminases increased,
sepsis, bronchitis, and pneumonitis. Dosage interruptions due to an
adverse reaction occurred in 23% of patients who received JEMPERLI.
Adverse reactions that required dosage interruption in >=1% of
patients who received JEMPERLI were anaemia, diarrhoea, increased
lipase, and pyrexia.
Please see full Prescribing 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.us.gsk.com/about-us .
GSK enquiries:
Media enquiries: Simon Steel +44 (0) 20 8047 (London)
5502
Tim Foley +44 (0) 20 8047 (London)
5502
Kristen Neese +1 804 217 8147 (Philadelphia)
Kathleen Quinn +1 202 603 5003 (Washington
DC)
Analyst/Investor James Dodwell +44 (0) 20 8047 (London)
enquiries: 2406
Sonya Ghobrial +44 (0) 7392 (Consumer)
784784
Mick Readey +44 (0) 7990 (London)
339653
Jeff McLaughlin +1 215 751 7002 (Philadelphia)
Frannie DeFranco +1 215 751 4855 (Philadelphia)
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 in the Company's
Annual Report on Form 20-F for 2020 and any impacts of the COVID-19
pandemic.
Registered in England & Wales:
No. 3888792
Registered Office:
980 Great West Road
Brentford, Middlesex
TW8 9GS
[i] CancerMPact(R) Patient Metric, Kantar. Available from
www.cancermpact.com. Accessed 18 March 2020.
[ii] NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines(R) ) for Uterine Neoplasms V1.2020. (c) National
Comprehensive Cancer Network, Inc. 2020. All rights reserved.
Accessed 17 April 2020. SGO Clinical Practice Endometrial Cancer
Working Group.
[iii] Burke WM, Orr J, Leitao M, et al. Endometrial Cancer: a
review and current management strategies: part II. Gynecol Oncol.
2014;134(2):393-402.
[iv] Brooks RA, Flemming GF, Lastra RR, et al. Current
recommendations and recent progress in endometrial cancer. CA
Cancer J Clin. 2019;69(4):258-279.
[v] Oaknin A, Tinker AV, Gilbert L, et al. Clinical activity and
safety of the anti-programmed death 1 monoclonal antibody
dostarlimab for patients with recurrent or advanced mismatch
repair-deficient endometrial cancer: a nonrandomized phase 1
clinical trial. JAMA Oncol. 2020;6(11):1766-1772.
[vi] Le DT, Durham JN Smith KN, et al. Mismatch repair
deficiency predicts response of solid tumors to PD-1 blockade.
Science. 2017;357(6349):409-413.
[vii] Lorenzi M, Amonkar M, Zhang J, et al. Epidemiology of
microsatellite instability high (MSI-H) and deficient mismatch
repair (dMMR) in solid tumor: a structured literature review.
Journal of Oncology. 2020; Article ID 18079.
[viii] Backes FJ, Haag J, Cosgrove CS, et al. Mismatch repair deficiency identifies patients with high-intermediate risk (HIR) endometrioid endometrial cancer at the highest risk of recurrence: a prognostic biomarker. Cancer. 2019;125(3):398-405.
[ix] Endometrial Cancer Treatment (PDQ(R) ) - Health
Professional Version. National Cancer Institute.
https://www.cancer.gov/types/uterine/hp/endometrial-treatment-pdq .
Accessed May 2020.
[x] Cancer Facts & Figures 2021. American Cancer Society.
Accessed 30 March 2021.
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf
.
[xi] Fung-Kee-Fung M, Dodge J, Elit L, et al. Follow-up after
primary therapy for endometrial cancer: a systematic review.
Gynecol Oncol. 2006;101(3):520-529 .
This information is provided by RNS, the news service of the
London Stock Exchange. RNS is approved by the Financial Conduct
Authority to act as a Primary Information Provider in the United
Kingdom. Terms and conditions relating to the use and distribution
of this information may apply. For further information, please
contact rns@lseg.com or visit www.rns.com.
RNS may use your IP address to confirm compliance with the terms
and conditions, to analyse how you engage with the information
contained in this communication, and to share such analysis on an
anonymised basis with others as part of our commercial services.
For further information about how RNS and the London Stock Exchange
use the personal data you provide us, please see our Privacy
Policy.
END
REABIGDSIXDDGBD
(END) Dow Jones Newswires
April 23, 2021 02:00 ET (06:00 GMT)
Gsk (LSE:GSK)
Historical Stock Chart
From Mar 2024 to Apr 2024
Gsk (LSE:GSK)
Historical Stock Chart
From Apr 2023 to Apr 2024