LONDON, April 22, 2021 /PRNewswire/ -- 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. JEMPERLI 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 tumor 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
JEMPERLI by the FDA has the potential to transform the treatment
landscape for these women and demonstrates our continued commitment
to helping patients with gynecologic 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 tumor
typesvi,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 Gynecologic Oncology at Levine Cancer Institute, Atrium
Health, and investigator on the GARNET study, noted: "The
approval of JEMPERLI 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, multicenter,
non-randomized, 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 program, and JEMPERLI 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 JEMPERLI 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%), diarrhea (26%), anemia
(24%) and constipation (20%). The most common Grade 3 or 4 adverse
reactions (≥2%) were anemia and transaminases
increase. JEMPERLI was permanently discontinued due to adverse
reactions in 5 (4.8%) patients. No deaths attributed to JEMPERLI
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 gynecologic
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 JEMPERLI brings
a new treatment option to an underserved patient population."
GSK is also studying JEMPERLI for endometrial cancer in earlier
treatment lines and in combination with other therapeutic agents
for patients with advanced solid tumors or metastatic cancer as we
work to expand our oncology pipeline and reinforce our portfolio of
cancer treatments.
Making our products affordable and accessible
GSK is
actively involved in creating solutions that allow patients to have
access to new scientific breakthroughs. We remain committed to
helping patients access GSK medications and have a long history of
providing patient assistance programs. Patients and healthcare
professionals can access more information about our oncology
specific resources on insurance coverage and financial support at:
www.TogetherwithGSKOncology.com or call: 1-844-4GSK-ONC
(1-844-447-5662).
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 therapy.ix Nearly 60,000 new cases of
endometrial cancer are expected in the US in 2021, making
endometrial cancer the most common gynecologic 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 tumors. 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
tumor basket cohort (cohort F), and platinum-resistant ovarian
cancer without BRCA mutations (cohort G). GARNET is still
enrolling patients.
About JEMPERLI (dostarlimab-gxly)
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.xiii In addition to
GARNET, JEMPERLI 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 tumors or metastatic cancer.
JEMPERLI 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: 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, commercialization, and manufacture of each
of these Products under the Agreement.
Important Safety Information for JEMPERLI
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 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
-
- 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
-
- 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
-
- 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.
- 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.
- 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.
- 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
-
- 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.
-
- Nervous System: Meningitis, encephalitis, myelitis and
demyelination, myasthenic syndrome/myasthenia gravis,
Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy
- Cardiac/Vascular: Myocarditis, pericarditis,
vasculitis
- 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.
- Gastrointestinal: Pancreatitis, including increases in
serum amylase and lipase levels, gastritis, duodenitis
- Musculoskeletal and Connective Tissue:
Myositis/polymyositis, rhabdomyolysis and associated sequelae
including renal failure, arthritis, polymyalgia rheumatica
- Endocrine: Hypoparathyroidism
- Other (Hematologic/Immune): Hemolytic anemia, aplastic
anemia, 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%), diarrhea (26%),
anemia (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 anemia, diarrhea, increased lipase, and
pyrexia.
Please see full Prescribing Information
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i
CancerMPact® Patient Metric, Kantar. Available from
www.cancermpact.com. Accessed 18 March 2020.
|
ii NCCN
Clinical Practice Guidelines in Oncology (NCCN
Guidelines®) for Uterine Neoplasms V1.2020. © 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®) – 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.
|
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