NEW ZEALAND DATA SHEET

1. PRODUCT NAME
Jemperli 500 mg/10 mL concentrate for solution for infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each mL of concentrate for solution for infusion contains 50 mg of dostarlimab.

One vial of 10 mL concentrate for solution for infusion contains 500 mg of dostarlimab (50
mg/mL).

Dostarlimab is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA

technology.

For the full list of excipients, see section 6.1 List of excipients.

3. PHARMACEUTICAL FORM
Concentrate for solution for infusion (sterile concentrate).
Dostarlimab is a clear to slightly opalescent colourless to yellow solution, free from visible
particles.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications

Jemperli is indicated in combination with platinum-containing chemotherapy for the treatment

of adult patients with primary advanced or recurrent mismatch repair deficient
(dMMR)/microsatellite instability-high (MSI-H) endometrial cancer (EC).
Jemperli is indicated as monotherapy for the treatment of adult patients with recurrent or
advanced mismatch repair deficient (dMMR) endometrial cancer (EC) that has progressed
on or following prior treatment with a platinum-containing regimen.
4.2 Dose and method of administration

Dostarlimab in combination with chemotherapy

When dostarlimab is administered in combination with chemotherapy, refer to the full Data
Sheet for the combination products (see also section 5.1 PHARMACODYNAMIC
PROPERTIES, Clinical efficacy and safety)

The recommended dose as combination therapy is 500 mg dostarlimab administered as an

intravenous infusion over 30 minutes every 3 weeks for 6 doses, followed by 1000 mg every
6 weeks for all cycles thereafter.
The dosage regimen in combination with chemotherapy is presented in Table 1.

1
Table 1. Dosage regimen for dostarlimab in combination with chemotherapy

500 mg once every 3 weeks 1000 mg once every 6 weeks

in combination with chemotherapya until disease progression or
unacceptable toxicity
(1 Cycle = 3 weeks)
(1 Cycle = 6 weeks)
Cycle Cycle Cycle Cycle Cycle Cycle Cycle Cycle Cycle Cycle Continue
1 2 3 4 5 6 7 8 9 dosing
Week 1 4 7 10 13 16 19 25 31 Q6W

3 weeks between Cycle 6 and Cycle 7

a
Administer dostarlimab prior to chemotherapy on the same day.

Administration of dostarlimab should continue according to the recommended dose and

schedule until disease progression or unacceptable toxicity.

Dostarlimab monotherapy

The recommended dose as monotherapy is 500 mg dostarlimab administered as an

intravenous infusion over 30 minutes every 3 weeks for 4 cycles followed by 1,000 mg every
6 weeks for all cycles thereafter.

The dosage regimen as monotherapy is presented in Table 2.

Table 2. Dosage regimen for dostarlimab as monotherapy

500 mg once every 3 weeks 1,000 mg once every 6 weeks until
disease progression or unacceptable
(1 Cycle = 3 weeks)
toxicity
(1 Cycle = 6 weeks)
Cycle Cycle Cycle Cycle Cycle Cycle Cycle Cycle Continue
1 2 3 4 6 7 dosing
5
Week 1 4 7 10 13 19 25 Q6W

3 weeks between Cycle 4 and Cycle 5

Administration of dostarlimab should continue according to the recommended dose and

schedule until disease progression or unacceptable toxicity.

Dose modifications

Dose reduction is not recommended. Dosing delay or discontinuation may be required based
on individual safety and tolerability. Recommended modifications to manage adverse
reactions are provided in Table 3. Detailed guidelines for the management of immune-
related adverse reactions and infusion-related reactions are described in Section 4.4 Special
Warnings and Precautions for use.

2
Table 3. Recommended dose modifications for dostarlimab
Immune-related adverse Severity gradea Dose modification
reactions

2 or 3 Withhold dose. Restart dosing

when toxicity resolves to Grade 0
Colitis or 1.

4 Permanently discontinue.

Grade 2 (ASTb or ALTc

Withhold dose. Restart dosing
> 3 and up to 5 × ULNd
when toxicity resolves to Grade 0
or total bilirubin > 1.5
or 1.
and up to 3 × ULN)

Hepatitis
Grade ≥3 (AST or ALT
Permanently discontinue (see
> 5 × ULN or total
exception below)e
bilirubin > 3 × ULN)

Withhold dose. Restart dosing in

Type 1 diabetes mellitus
3 or 4 (hyperglycaemia) appropriately managed, clinically
(T1DM)
and metabolically stable patients.

Withhold dose. Restart dosing

2, 3 or 4 when toxicity resolves to Grade 0
Hypophysitis or adrenal
or 1. Permanently discontinue for
insufficiency
recurrence or worsening while on
adequate hormonal therapy.

Withhold dose. Restart dosing

Hypothyroidism or
when toxicity resolves to Grade 0
hyperthyroidism 3 or 4 or 1.
Withhold dose. Restart dosing
when toxicity resolves to Grade 0
2
Pneumonitis or 1. If Grade 2 recurs,
permanently discontinue.

3 or 4 Permanently discontinue.
Withhold dose. Restart dosing
2 when toxicity resolves to Grade 0
Nephritis or 1.
3 or 4 Permanently discontinue.
Withhold dose for any grade.
Exfoliative dermatologic
Restart dosing if not confirmed
conditions (e.g. SJS, TEN, Suspected
and when toxicity resolves to
DRESS)
Grade 0 or 1.

3
 Table 3. Recommended dose modifications for dostarlimab
Immune-related adverse Severity gradea Dose modification
reactions

Confirmed Permanently discontinue.

Myocarditis 2, 3 or 4 Permanently discontinue.

Severe neurological 2, 3 or 4 Permanently discontinue.

toxicities (myasthenic
syndrome/myasthenia
gravis, Guillain-Barré
syndrome, encephalitis,
transverse myelitis)
Withhold dose. Restart dosing
Other immune-related 3 when toxicity resolves to Grade 0
adverse reactions involving or 1.
a major organ
4 Permanently discontinue.
Recurrence of immune-
related adverse reactions
after resolution to ≤ Grade 1 3 or 4 Permanently discontinue.
(except for pneumonitis,
see above)
Other adverse reactions Severity gradea Dose modification

Withhold dose. If resolved within

1 hour of stopping, may be
restarted at 50% of the original
infusion rate, or restart when
2
Infusion-related reactions symptoms resolve with pre-
medication. If Grade 2 recurs with
adequate premedication,
permanently discontinue.
3 or 4 Permanently discontinue.
a Toxicity
graded per National Cancer Institute Common Terminology Criteria for Adverse Events
(CTCAE) version 5.0.
b AST = aspartate aminotransferase
c ALT = alanine aminotransferase
d ULN = upper limit of normal
e Forpatients with liver metastases who begin treatment with Grade 2 AST or ALT, if AST or ALT
increases by ≥50% relative to baseline and lasts for at least 1 week, then treatment should be
discontinued.

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Special Populations

Elderly

No dose adjustment is recommended for patients who are 65 years of age or over. There
are limited clinical data with dostarlimab in patients 75 years of age or over (see section 5.1
PHARMACODYNAMIC PROPERTIES).

Renal impairment

No dose adjustment is recommended for patients with mild or moderate renal impairment.
There are limited data in patients with severe renal impairment or end-stage renal disease
undergoing dialysis (see Section 5.2 PHARMACOKINETIC PROPERTIES).

Hepatic impairment

No dose adjustment is recommended for patients with mild hepatic impairment. There are
limited data in patients with moderate or severe hepatic impairment (see Section 5.2
PHARMACOKINETIC PROPERTIES).

Paediatric Population

The safety and efficacy of dostarlimab in children and adolescents aged under 18 years
have not been established. No data are available.

Method of administration

Preparation
Parenteral medicinal products should be inspected visually for particulate matter and
discolouration prior to administration. Dostarlimab is a slightly opalescent colourless to
yellow solution. Discard the vial if visible particles are observed.
Dilution
For instructions on dilution of the medicine before administration, see section 6.6.
Administration
Dostarlimab is for intravenous infusion only. Dostarlimab should be administered by
intravenous infusion using an intravenous infusion pump over 30 minutes by a health care
practitioner.
Dostarlimab must not be administered as an intravenous push or bolus injection.
Dostarlimab is compatible with an IV bag made of polyvinyl chloride (PVC) with or without
di(2-ethylhexyl) phthalate (DEHP), ethylene vinyl acetate, polyethylene (PE), polypropylene
(PP) or polyolefin blend (PP+PE), and a syringe made from PP. Infusion tubing should be
made of PVC, platinum cured silicon or PP; fittings made from PVC or polycarbonate and
needles made from stainless steel. A 0.2 or 0.22 micron in-line polyethersulfone (PES) filter
must be used during administration of dostarlimab.

4.3 Contraindications

None

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4.4 Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the tradename and the
batch number of the administered product should be clearly recorded.

Immune-related 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 dostarlimab. 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. Monitor for symptoms and signs of
immune-related adverse reactions. Evaluate haematological and clinical chemistries,
including liver, kidney and thyroid function tests, 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, dostarlimab should be withheld or
permanently discontinued and corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) or
other appropriate therapy administered (see below and section 4.2 DOSING AND
ADMINISTRATION, Dose modification). Upon improvement to Grade 0 or 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. Institute hormone replacement therapy for endocrinopathies as warranted.
Dostarlimab 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 Table 3.

Immune-related pneumonitis
Pneumonitis has been reported in patients receiving dostarlimab (see Section 4.8 ADVERSE
EFFECTS). 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 dostarlimab treatment modifications and
corticosteroids (see Section 4.2 DOSING AND ADMINISTRATION).

Immune-related colitis
Dostarlimab can cause immune-related colitis (see Section 4.8 ADVERSE EFFECTS).
Monitor patients for signs and symptoms of colitis and manage with dostarlimab treatment
modifications, anti-diarrhoeal agents and corticosteroids (see Section 4.2 DOSING AND
ADMINISTRATION).

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Immune-related hepatitis
Dostarlimab can cause immune-related hepatitis. Monitor patients for changes in liver
function periodically as indicated based on clinical evaluation and manage with dostarlimab
treatment modifications and corticosteroids (see Section 4.2 DOSING AND
ADMINISTRATION).

Immune-related endocrinopathies
Immune-related endocrinopathies, including hypothyroidism, hyperthyroidism, thyroiditis,
hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis and adrenal insufficiency, have
been reported in patients receiving dostarlimab (see Section 4.8 ADVERSE EFFECTS).
Hypothyroidism and hyperthyroidism
Immune-related hypothyroidism and hyperthyroidism (including thyroiditis) occurred in
patients receiving dostarlimab, and hypothyroidism may follow hyperthyroidism.
Patients should be monitored for abnormal thyroid function tests prior to and
periodically during treatment and as indicated based on clinical evaluation. Immune-
related hypothyroidism and hyperthyroidism (including thyroiditis) should be managed
as recommended in Section 4.2 DOSING AND ADMINISTRATION.

Adrenal insufficiency
Immune-related adrenal insufficiency occurred in patients receiving dostarlimab.
Patients should be monitored for clinical signs and symptoms of adrenal insufficiency.
For symptomatic adrenal insufficiency, patients should be managed as recommended
in Section 4.2 DOSING AND ADMINISTRATION.

Immune-related nephritis
Dostarlimab can cause immune-related nephritis (see Section 4.8 ADVERSE EFFECTS).
Monitor patients for changes in renal function and manage with dostarlimab treatment
modifications and corticosteroids (see Section 4.2 DOSING AND ADMINISTRATION).

Immune-related rash
Immune-related rash has been reported in patients receiving dostarlimab, including
pemphigoid (see Section 4.8 ADVERSE EFFECTS). Patients should be monitored for signs
and symptoms of rash. Exfoliative dermatologic conditions should be managed as
recommended (see 4.2 DOSING AND ADMINISTRATION). Events of Stevens-Johnson
Syndrome (SJS), toxic epidermal necrolysis (TEN) or drug rash with eosinophilia and
systemic symptoms (DRESS) have been reported in patients treated with PD-1 inhibitors.
Caution should be used when considering the use of dostarlimab in a patient who has
previously experienced a severe or life-threatening skin adverse reaction on prior treatment
with other immune-stimulatory anticancer agents.

Other immune-related adverse reactions

Given the mechanism of action of dostarlimab other potential immune-related adverse
reactions may occur. Clinically significant immune-related adverse reactions reported in less
than 1% of patients treated with dostarlimab as monotherapy in clinical trials include
encephalitis, autoimmune haemolytic anaemia, uveitis, and iridocyclitis. Patients should be

7
monitored for signs and symptoms of immune-related adverse reactions and managed as
described in Section 4.2 DOSING AND ADMINISTRATION.

Transplant-related adverse reactions

Solid organ transplant rejection
Solid organ transplant rejection has been reported in the postmarketing setting in patients
treated with PD-1 inhibitors. Treatment with dostarlimab may increase the risk of rejection in
solid organ transplant recipients. The benefit of treatment with dostarlimab versus the risk of
possible organ rejection should be considered in these patients.

Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT)

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
Dostarlimab can cause infusion-related reactions, which can be severe (see Section 4.8
ADVERSE EFFECTS). For severe (Grade 3) or life-threatening (Grade 4) infusion-related
reactions, stop infusion and permanently discontinue Dostarlimab (see Section 4.2 DOSING
AND ADMINISTRATION).

4.5 Interaction with other medicines and other forms of interaction

No drug-drug interaction studies have been conducted with dostarlimab. Monoclonal

antibodies (mAbs) such as dostarlimab are not substrates for cytochrome P450 or drug
transporters. Additionally, pharmacokinetic (PK) drug-drug interaction of dostarlimab with
small molecule drugs is not expected.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no available data on the use of dostarlimab in pregnant women. Animal
reproduction studies have not been conducted with dostarlimab to evaluate its effect on
reproduction and fetal development. Based on its mechanism of action, dostarlimab can
cause fetal harm when administered to a pregnant woman. Animal models link the PD-1/PD-
L1 signalling pathway with maintenance of pregnancy through induction of maternal immune
tolerance to fetal tissue. Human IgG4 immunoglobulins (IgG4) are known to cross the
placental barrier; therefore, dostarlimab has the potential to be transmitted from the mother
to the developing fetus. Advise women of the potential risk to a fetus.

8
Dostarlimab is not recommended during pregnancy. Women of childbearing potential should
use highly effective contraception during treatment with dostarlimab and for 4 months after
the last dose.

Breast-feeding

There is no information regarding the presence of dostarlimab in human milk, or its effects
on the breastfed child or on milk production. Because of the potential for serious adverse
reactions in breastfed children, advise women not to breastfeed during treatment and for 4
months after the last dose of dostarlimab.

Fertility

Fertility studies have not been conducted with dostarlimab. No effects on male and female
reproductive organs were observed in a 3-month repeat dose toxicity study in cynomolgus
monkeys at ≤100 mg/kg/week IV, resulting in exposures (AUC) at least 28 times that
expected in patients; however, these results may not be predictive of clinical risk because of
the immaturity of the reproductive system of animals used in the study.

4.7 Effects on ability to drive and use machines

Dostarlimab has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Summary of the safety profile

The safety of dostarlimab as monotherapy has been evaluated in 605 patients with recurrent
or advanced solid tumours, including 314 patients with endometrial cancer and 291 patients
with other advanced solid tumours, in the GARNET study. Patients received doses of
dostarlimab 500 mg every 3 weeks for 4 cycles, followed by 1000 mg every 6 weeks for all
cycles thereafter.
The safety of dostarlimab in combination with chemotherapy has been evaluated in 241
patients with primary advanced or recurrent endometrial cancer in the RUBY study. Patients
received doses of dostarlimab 500 mg every 3 weeks for 6 cycles, followed by 1000 mg
every 6 weeks for all cycles thereafter.
Adverse reactions observed in patients who received dostarlimab monotherapy in the
GARNET study are listed in Table 4. Adverse reactions observed in patients who received
dostarlimab in combination with chemotherapy in the RUBY study, as well as additional
adverse reactions identified from other clinical trials in patients with solid tumors receiving
dostarlimab in combination with various types of anticancer therapies are shown in Table 5
Adverse reactions known to occur with dostarlimab or with combination therapy components
when given alone may occur during treatment with these medicinal products in combination,
even if these reactions were not reported in clinical studies with combination therapy.
When dostarlimab is administered in combination, refer to the local label for the respective
combination therapy component prior to initiation of treatment.

9
Tabulated list of adverse reactions

Adverse reactions are presented by system organ class and by frequency. Frequencies are
defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to <
1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be
estimated from the available data).

Table 4. Adverse reactions in patients with solid tumours treated with dostarlimab
monotherapy

System Organ Dostarlimab All Grades Grades 3-4

Class/Adverse Reaction monotherapy n (%) n (%)
Blood and lymphatic
system disorders
Anaemia Very common 173 (28.6) 59(9.8)
Autoimmune haemolytic
anaemia Uncommon 1 (0.2) 1 (0.2)
Endocrine disorders
Hypothyroidism Very common 68 (11.2)a 0
Hyperthyroidism Common 32 (5.3) 1 (0.2)
Adrenal insufficiency Common 8 (1.3) 4 (0.7)
Thyroiditis Uncommon 4 (0.7)b 0
Hypophysitis Uncommon 3 (0.5)c 0
Metabolism and
nutrition disorders
Type 1 diabetes mellitus Uncommon 1 (0.2) 1 (0.2)
Diabetic ketoacidosis Uncommon 1 (0.2) 1 (0.2)
Nervous system
disorders
Encephalitis Uncommon 2 (0.3) 2 (0.3)
Myasthenia gravis Uncommon 1 (0.2) 0
Eye disorders
Uveitis Uncommon 2 (0.3)d 0
Respiratory, thoracic
and mediastinal
disorders
Pneumonitis Common 25 (4.1)e 7 (1.2)f
Gastrointestinal
disorders Very common 157 (26) 8 (1.3)
Diarrhoea Very common 156 (25.8) 13 (2.1)
Nausea Very common 115 (19.0) 10 (1.7)
Vomiting Common 13 (2.1)g 5 (0.8)h
Colitis Common 7 (1.2)i 6 (1.0)i
Pancreatitis Common 6 (1.0) 1 (0.2)
Gastritis Uncommon 1 (0.2) 1 (0.2)
Oesophagitis

10
 System Organ Dostarlimab All Grades Grades 3-4
Class/Adverse Reaction monotherapy n (%) n (%)
Hepatobiliary disorders
Hepatitis Common 7 (1.2)j 4 (0.7) j
Skin and subcutaneous
tissue disorders
Rash Very common 126 (20.8)k 9 (1.5)l
Pruritus Very common 86 (14.2) 2 (0.3)
Musculoskeletal and
connective tissue
disorders
Myalgia Common 46 (7.6) 0
Immune-mediated arthritis Uncommon 3 (0.5) 1 (0.2)
Polymyalgia rheumatica Uncommon 2 (0.3) 0
Immune-mediated Uncommon 1 (0.2) 1 (0.2)
myositis
Renal and urinary
disorders
Nephritis Uncommon 4 (0.7)m 0
General disorders and
administration site
conditions
Pyrexia Very common 75 (12.4) 1 (0.2)
Chills Common 24 (4.0) 1 (0.2)
Investigations
Transaminases increased Very common 90 (14.9)n 20 (3.3) o
Injury, poisoning and
procedural
complications Common 8 (1.3)p 1 (0.2)
Infusion-related reaction
a Includes hypothyroidism and autoimmune hypothyroidism
b Includes thyroiditis and autoimmune thyroiditis
c Includes hypophysitis and lymphocytic hypophysitis
d Includes uveitis and iridocyclitis
e Includes pneumonitis, interstitial lung disease and immune-mediated lung disease
f Includes pneumonitis and interstitial lung disease.
g Includes colitis, enterocolitis and immune-mediated enterocolitis
h Includes colitis and immune-mediated enterocolitis
i Includes pancreatitis and pancreatitis acute
j Includes hepatitis, autoimmune hepatitis and hepatic cytolysis
k
Includes rash, rash maculopapular, erythema, rash macular, rash pruritic, rash erythematous,
rashpapular, erythema multiforme, skin toxicity, drug eruption, toxic skin eruption, exfoliative rash
and pemphigoid
l Includes rash, rash maculo-papular and drug eruption

11
m Includes nephritis and tubulointerstitial nephritis
n Includesalanine aminotransferase increased, aspartate aminotransferase increased, transaminases
increased and hypertransaminasaemia
o Includes
alanine aminotransferase increased, aspartate aminotransferase increased and
transaminases increased.
p Includes infusion-related reaction and hypersensitivity.

Table 5. Adverse reactions in patients with solid tumours treated with dostarlimab in
combination therapy

System Organ Dostarlimab All Grades Grades 3-4

Class/Adverse Reaction combination
n (%) n (%)
therapy
Endocrine disorders
Hypothyroidism Very common 35 (14.5)a 0
Hyperthyroidism Common 10 (4.1) 1 (0.4)
Adrenal insufficiency Uncommon 2 (0.8) 1 (0.4)
Thyroiditis Uncommon 1 (0.4) 0
Metabolism and nutrition
disorders
Type 1 diabetes mellitus Uncommon 1 (0.4) 1 (0.4)

Nervous system disorders

Myasthenic syndrome Uncommon 1 (0.1)b 1 (0.1)b
Eye disorders
Uveitis Uncommon 1 (0.4) 1 (0.4)
Cardiac disorders
Myocarditis Uncommon 2 (0.2)c 2 (0.2)c
Respiratory, thoracic and
mediastinal disorders
Pneumonitis Common 5 (2.1) 1 (0.4)
Gastrointestinal disorders
Colitis Common 4 (1.1)d 3 (0.8)d
Pancreatitis Common 3 (1.2) 2 (0.8)
b
Immune mediated gastritis Uncommon 1 (0.1) 1 (0.1)b
Vasculitis gastrointestinal Uncommon 1 (0.1)b 1 (0.1)b
Skin and subcutaneous
tissue disorders
Rash Very common 85 (34.9)e 15 (6.2)e
Dry skin Very common 25 (10.4) 0

12
 System Organ Dostarlimab All Grades Grades 3-4
Class/Adverse Reaction combination
n (%) n (%)
therapy
Musculoskeletal and
connective tissue
disorders
Immune-mediated arthritis Uncommon 1 (0.4) 1 (0.4)
Myositis Uncommon 2 (0.4)f 1 (0.2)f
General disorders and
administration site
conditions
Pyrexia Very common 29 (12.0) 0
Systemic inflammatory
response syndrome Uncommon 2 (0.4)f 2 (0.4)f
Investigations
Alanine aminotransferase
increased Very common 31 (12.9) 5 (2.1)
Aspartate aminotransferase
increased Very common 29 (12.0) 5 (2.1)
a Includes hypothyroidism and immune-mediated hypothyroidism
b Reported from ongoing blinded trial of dostarlimab in combination; estimated frequency category
cIncludes myocarditis (combination with chemotherapy) and immune-mediated myocarditis from
ongoing blinded trial of dostarlimab in combination; estimated frequency category
d Includes colitis (combination with chemotherapy) and enteritis reported from ongoing trials of
dostarlimab in combination
e Includes rash and rash maculo-papular
f Reported in ongoing trial of dostarlimab in combination

Description of selected adverse reactions

Other adverse events

Table 6 summarises other adverse events that occurred in 10% or more of patients with solid
tumours treated with dostarlimab monotherapy in the GARNET study. Fatigue and asthenia
are the only adverse events reported in at least 20% of patients. Grade 4 events included
asthenia (N=1 patient, 0.2%) and dyspnoea (N=2 patients, 0.3%).

Table 6. Other adverse events in ≥10% of patients with solid tumours treated with
dostarlimab monotherapy
System Organ Class/Adverse Event All Grades Grades 3-4
n (%) n (%)

Gastrointestinal disorders

Constipation 109 (18.0) 4 (0.7)

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 System Organ Class/Adverse Event All Grades Grades 3-4
n (%) n (%)

Abdominal pain 106 (17.5) 21 (3.5)

General disorders and administration

site conditions

Fatigue 155 (25.6) 17 (2.8)

Asthenia 126 (20.8) 13 (2.1)

Infections and infestations

Urinary tract infection 86 (14.2) 9 (1.5)

Musculoskeletal and connective

tissue disorders

Arthralgia 103 (17.0) 5 (0.8)

Back pain 78 (12.9) 10 (1.7)

Metabolism and nutrition disorders

Decreased appetite 108 (17.9) 6 (1.0)

Nervous system disorders

Headache 61 (10.1) 0

Respiratory, thoracic and mediastinal

disorders

Cough 96 (15.9) 1 (0.2)

Dyspnoea 79 (13.1) 20 (3.3)

Table 7 summarises other adverse events that occurred in 10% or more of patients with
endometrial cancer treated with dostarlimab in combination with chemotherapy in the RUBY
study. Grade 4 events included neutrophil count decreased (N=9 patients, 3.7%), neutropenia
(N=8 patients, 3.3%), thrombocytopenia and white blood cell count decreased (N=3 patients
each, 1.2%), and pruritus, hypomagnesaemia, hypokalaemia, blood creatinine increased,
hypertension and infusion related reaction (N=1 patient each, 0.4%).

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Table 7. Other adverse events in ≥10% of patients with endometrial cancer treated with
dostarlimab in combination with chemotherapy

System Organ Class/Adverse events All Grades Grades 3-4

n (%) n (%)

Gastrointestinal disorders

Nausea 130 (53.9) 7 (2.9)

Constipation 83 (34.4) 1 (0.4)

Diarrhoea 75 (31.1) 4 (1.7)
Vomiting 48 (19.9) 4 (1.7)
Abdominal pain 38 (15.8) 4 (1.7)
Dyspepsia 26 (10.8) 0

Nervous system disorders

Neuropathy peripheral 106 (44.0) 5 (2.1)
Peripheral sensory neuropathy 51 (21.2) 6 (2.5)
Headache 38 (15.8) 1 (0.4)
Dizziness 36 (14.9) 0
Dysgeusia 27 (11.2) 0

General disorders and administration

site conditions

Fatigue 125 (51.9) 4 (1.7)

Oedema peripheral 30 (12.4) 0

Skin and subcutaneous tissue

disorders
Alopecia 129 (53.5) 0
Pruritus 47 (19.5) 1 (0.4)

Infections and infestations

Urinary tract infection 42 (17.4) 6 (2.5)

Musculoskeletal and connective

tissue disorders

Arthralgia 86 (35.7) 2 (0.8)

Myalgia 63 (26.1) 0
Back pain 36 (14.9) 1 (0.4)

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 System Organ Class/Adverse events All Grades Grades 3-4
n (%) n (%)
Pain in extremity 29 (12.0) 1 (0.4)

Metabolism and nutrition disorders

Decreased appetite 52 (21.6) 5 (2.1)
Hypomagnesaemia 52 (21.6) 2 (0.8)
Hypokalaemia 47 (19.5) 12 (5.0)

Investigations
Neutrophil count decreased 33 (13.7) 20 (8.3)
White blood cell count decreased 32 (13.3) 16 (6.6)\
Platelet count decreased 31 (12.9) 5 (2.1)
Blood creatinine increased 27 (11.2) 2 (0.8)

Blood and lymphatic system

disorders
Anaemia
91 (37.8) 36 (14.9)
Neutropenia
33 (13.7) 23 (9.5)
Thrombocytopenia
25 (10.4) 7 (2.9)

Respiratory, thoracic and mediastinal

disorders
Dyspnoea 44 (18.3) 3 (1.2)
Cough 32 (13.3) 0

Vascular disorders
Hypertension 32 (13.3) 17 (7.1)

Injury, poisoning and

procedural complications
Infusion related reactions 33 (13.7) 2 (0.8)

Psychiatric disorders
Insomnia 39 (16.2) 0

Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. The detection of
antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralising antibody) positivity in
an assay may be influenced by several factors including assay methodology, sample
handling, timing of sample collection, concomitant medications, and underlying disease. For

16
these reasons, comparison of the incidence of antibodies to dostarlimab in the studies
described below with the incidence of antibodies in other studies or to other products may be
misleading.
In the GARNET study, anti-drug antibodies (ADA) were tested in 384 patients who received
dostarlimab monotherapy and the incidence of dostarlimab treatment-emergent ADAs was
2.1%. Neutralising antibodies were detected in 1.0% of patients.
Co-administration with chemotherapy did not affect dostarlimab immunogenicity. In the
RUBY study, of the 225 patients who were treated with dostarlimab in combination with
chemotherapy and evaluable for the presence of ADAs, there was no incidence of
dostarlimab treatment-emergent ADA or treatment emergent neutralising antibodies.
In the patients who developed anti-dostarlimab antibodies in either study, there was no
evidence of altered pharmacokinetics, efficacy or safety of dostarlimab. Because of the small
number of patients who developed ADAs, the impact of immunogenicity on the efficacy and
safety of dostarlimab is inconclusive.

Paediatric population

The safety and efficacy of dostarlimab in children and adolescents aged under 18 years
have not been established. No data are available.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It

allows continued monitoring of the benefit/risk balance of the medicine. Healthcare
professionals are asked to report any suspected adverse reactions via:
https://pophealth.my.site.com/carmreportnz/s/

4.9 Overdose

If overdose is suspected, the patient should be monitored for any signs or symptoms of
adverse reactions or effects, and appropriate standard of care measures should be instituted
immediately.
For advice on the management of overdose please contact the National Poisons Centre on
0800 POISON (0800 764766).

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Anti-neoplastic agents, monoclonal antibodies, ATC code:

L01FF07

Mechanism of action

Dostarlimab is an anti-programmed cell death protein-1 (PD-1) immunoglobulin G4 (IgG4)

humanised monoclonal antibody (mAb), derived from a stable Chinese hamster ovary (CHO)
cell line.
Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells inhibits
T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some
tumours and signalling through this pathway can contribute to inhibition of active T-cell
immune surveillance of tumours. Dostarlimab is a humanised mAb of IgG4 isotype that binds
to PD 1, resulting in inhibition of binding to PD-L1 and PD-L2, releasing inhibition of PD-1

17
pathway-mediated immune response, including the anti-tumour immune response. In
syngeneic mouse tumour models, blocking PD-1 activity resulted in decreased tumour
growth.

Pharmacodynamic effects

Based on exposure efficacy and safety relationships, there are no clinically significant
differences in efficacy and safety within the exposure range attained under the
recommended therapeutic dosing regimen (500 mg administered intravenously every 3
weeks for 4 doses, followed by 1,000 mg every 6 weeks thereafter). Full receptor occupancy
as measured by both the direct PD-1 binding and IL-2 production functional assay was
maintained throughout the dosing interval at the recommended therapeutic dosing regimen.

Clinical efficacy and safety

RUBY: Randomised controlled study of combination therapy in treatment of primary

advanced or recurrent EC
The efficacy and safety of dostarlimab in combination with carboplatin-paclitaxel were
investigated in RUBY, a multicentre, randomised, double-blinded, placebo-controlled Phase
3 study conducted in patients with primary advanced or recurrent EC.
Patients were randomised (1:1) to receive dostarlimab 500 mg plus carboplatin AUC
5 mg/mL/min and paclitaxel 175 mg/m2 every 3 weeks for 6 cycles followed by dostarlimab
1000 mg every 6 weeks (n = 245) or placebo plus carboplatin AUC 5 mg/mL/min and
paclitaxel 175 mg/m2 every 3 weeks for 6 cycles followed by placebo every 6 weeks
(n = 249). Randomisation was stratified by MMR/MSI status, prior external pelvic
radiotherapy, and disease status (recurrent, primary Stage III, or primary Stage IV).
The key eligibility criteria for the study were International Federation of Gynaecology and
Obstetrics (FIGO) primary Stage III or Stage IV disease, including Stage IIIA to IIIC1 disease
with presence of evaluable or measurable disease per RECIST v.1.1, Stage IIIC1 patients
with carcinosarcoma, clear cell, serous, or mixed histology (containing ≥10%
carcinosarcoma, clear cell, or serous histology) regardless of presence of evaluable or
measurable disease on imaging, Stage IIIC2 or Stage IV disease regardless of presence of
evaluable or measurable disease. The study also included patients with first recurrent EC
with a low potential for cure by radiation therapy or surgery alone or in combination,
including patients who had first recurrent disease and were naïve to systemic anticancer
therapy or who had received prior neo-adjuvant/adjuvant systemic anticancer therapy and
had a recurrence or progressive disease ≥6 months after completing treatment (first
recurrence). Treatment continued for up to 3 years or until unacceptable toxicity, disease
progression or investigator decision. Assessment of tumour status was performed every
6 weeks through week 25, every 9 weeks through week 52 and every 12 weeks thereafter.
The primary efficacy outcome measures were progression-free survival (PFS), assessed by
the investigator according to RECIST v1.1 in subjects with dMMR/MSI-H primary advanced
or recurrent EC and in all subjects (overall ITT population) with primary advanced or
recurrent EC, and overall survival (OS) in all subjects (overall ITT population) with primary
advanced or recurrent EC. Secondary endpoints included objective response rate (ORR),
duration of response (DOR), and disease control rate (DCR) as assessed by blinded
independent central radiologists’ (BICR) review and investigator assessment according to
RECIST v1.1, and PFS2, defined as the time from treatment randomisation to the date of
assessment of progression on the first subsequent anticancer therapy following study
treatment or death by any cause, whichever was earlier.
A total of 494 patients with EC were evaluated for efficacy in the RUBY study. Baseline
demographics and characteristics of the overall study population were: median age 65 years

18
(51% age 65 years or older); 77% White, 12% Black, 3% Asian; and Eastern Cooperative
Oncology Group (ECOG) PS 0 (63%) or 1 (37%); and primary stage III 18.6%; primary stage
IV 33.6%; recurrent EC 47.8%.
The identification of dMMR/MSI-H tumour status was prospectively determined based on
local testing assays (IHC, PCR or NGS), or central testing (IHC) when no local result was
available.
Efficacy results are shown in Table 8 and Figures 1 and 2. The RUBY study demonstrated a
statistically significant improvement in PFS in patients randomised to dostarlimab plus
carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in both the overall ITT and
dMMR/MSI-H populations. At an interim analysis with 33% OS maturity (cut-off date 28 Sept
2022), OS results indicated a trend in favour of the dostarlimab plus carboplatin-paclitaxel
arm in the overall ITT population, with a 36% reduction in deaths and a HR of 0.64 (95% CI
0.46, 0.87; p=0.0021), which did not cross the p-value stopping boundary of 0.00177 for
statistical significance.

Table 8. Efficacy results in RUBY for patients with EC

Endpoint Overall populationa dMMR/MSI-H populationa

Dostarlimab + Placebo + Dostarlimab + Placebo +
carboplatin- carboplatin- carboplatin- carboplatin-
paclitaxel paclitaxel paclitaxel paclitaxel
(N=245) (N=249) (N=53) (N=65)
Primary endpoints
Progression free survival
(PFS)
Median in months (95% 11.8 (9.6, 17.1) 7.9 (7.6, 9.5) Not reached 7.7 (5.6, 9.7)
CI)b
Number (%) of patients 135 (55.1) 177 (71.1) 19 (35.8) 47 (72.3)
with event
Hazard ratio (95% CI)c 0.64 (0.51, 0.80) 0.28 (0.16, 0.50)
p-valueb <0.0001 <0.0001
Probability of PFS at 48.2 29.0 63.5 24.4
12 months (95% CI)d (41.3, 54.8) (23.0, 35.2) (48.5, 75.3) (13.9, 36.4)
Probability of PFS at 36.1 18.1 61.4 15.7
24 months (95% CI)d (29.3, 42.9) (13.0, 23.9) (46.3, 73.4) (7.2, 27.0)
Overall Survival (OS)e
Median in months Not reached Not reached Not reached Not reached
Number (%) of 65 (26.5) 100 (40.2) 7 (13.2) 24 (36.9)
patients with event
Hazard ratio (95% CI)c 0.64 (0.46, 0.87) 0.30 (0.13, 0.70)
p-valueb 0.0021 NAe
Probability of OS at 84.6 81.3 90.1 79.6
12 months (95% CI)d (79.2, 88.7) (75.7, 85.7) (77.8, 95.7) (67.5, 87.6)

19
 Endpoint Overall populationa dMMR/MSI-H populationa
Dostarlimab + Placebo + Dostarlimab + Placebo +
carboplatin- carboplatin- carboplatin- carboplatin-
paclitaxel paclitaxel paclitaxel paclitaxel
(N=245) (N=249) (N=53) (N=65)
Probability of OS at 71.3 56.0 83.3 58.7
24 months (95% CI)d (64.5, 77.1) (48.9, 62.5) (66.8, 92.0)
(43.4, 71.2)
Secondary endpoints
Objective response rate
(ORR)f
Number of participants 212 219 49 58
with evaluable disease
at baseline (n)
ORR, n (%) 149 (70.3) 142 (64.8) 38 (77.6) 40 (69.0)
(95% CI) (63.6, 76.3) (58.1, 71.2) (63.4, 88.2) (55.5, 80.5)
Complete response 53 (25.0) 43 (19.6) 15 (30.6) 12 (20.7)
rate, n (%)
Partial response rate, 96 (45.3) 99 (45.2) 23 (46.9) 28 (48.3)
n (%)
Duration of response
(DOR)f, g
Number of responder 149 142 38 40
(n)
Median in months 10.6 (8.2, 17.6) 6.2 (4.4, 6.7) Not reached 5.4 (3.9, 8.1)
(95% CI)h
Patients with duration 94 (63.1) 69 (48.6) 28 (73.7) 18 (45.0)
≥ 6 months, n (%)
Patients with duration 60 (40.3) 29 (20.4) 22 (57.9) 7 (17.5)
≥ 12 months, n (%)
PFS 2

Median in months NE 18.5 (14.9, NE 22.0 (13.4,

(95% CI)h 22.6) NE)
Hazard ratio 0.65 (0.50, 0.84) 0.37 (0.19, 0.73)
(95% CI)c
Probability of PFS2 at 57.4 (50.3, 41.4 (34.7, 76.6 (61.4, 48.3 (34.7,
24 months (95% CI)d 63.8) 48.0) 86.5) 60.6)
CI = Confidence interval; NA = not applicable; NE = not estimable
a Efficacy data with a median follow-up of 25 months (cut-off date 28 Sept 2022).
b One-sided p-value based on stratified log-rank test.
c Based on stratified Cox regression model.
d By Kaplan-Meier method.
e OS is a primary endpoint for the overall population only.

20
f Assessed by investigator according to RECIST v1.1.
g For patients with a partial or complete response.
h By Brookmeyer and Crowley method.

A pre-specified exploratory analysis of PFS was performed in patients with MMRp/MSS EC

(n = 192). The PFS HR was 0.76 (95% CI: 0.59, 0.98) with a median PFS of 9.9 months for
dostarlimab plus carboplatin-paclitaxel versus 7.9 months for placebo plus carboplatin-
paclitaxel.

Figure 1. Kaplan-Meier curve of progression-free survival per investigator assessment

in all patients (overall ITT population) with EC (RUBY study)
1.0 Dostarlimab + Carboplatin-Paclitaxel
Placebo + Carboplatin-Paclitaxel

0.8

0.6

0.4

0.2

0.0

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38

Dostarlimab +
245(0) 220(12) 197(25) 157(55) 130(80) 105(103) 94(110) 90(113) 84(118) 78(122) 66(127) 52(128) 34(131) 23(132) 22(132) 12(133) 2(134) 0(135)
Carboplatin-Paclitaxel
Placebo +
249(0) 219(14) 200(29) 144(77) 103(115) 74(141) 59(155) 57(157) 48(166) 42(170) 39(170) 32(172) 20(175) 14(176) 13(176) 5(177) 2(177) 1(177) 1(177) 0(177)
Carboplatin-Paclitaxel

21
Figure 2. Kaplan-Meier curve of progression-free survival per investigator assessment
in patients with dMMR/MSI-H EC (RUBY study)
1.0 Dostarlimab + Carboplatin-Paclitaxel
Placebo + Carboplatin-Paclitaxel

0.8

0.6

0.4

0.2

0.0

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34

Dostarlimab +
53(0) 48(3) 44(6) 39(10) 34(15) 31(17) 30(18) 29(19) 28(19) 27(19) 25(19) 19(19) 13(19) 9(19) 9(19) 4(19) 1(19) 0(19)
Carboplatin-Paclitaxel
Placebo +
65(0) 57(4) 54(7) 34(24) 26(32) 14(41) 12(43) 12(43) 11(44) 8(46) 8(46) 7(47) 4(47) 3(47) 3(47) 2(47) 1(47) 0(47)
Carboplatin-Paclitaxel

Patient-reported outcomes (PROs) were assessed using EORTC QLQ-C30. Throughout the
first 6 dosing cycles of the study, there were no clinically meaningful differences between
dostarlimab plus carboplatin-paclitaxel and placebo plus carboplatin-paclitaxel arms in
patient-reported symptoms, functioning, and health-related quality of life (assessed by a
difference of ≥10 points from the baseline assessment).

GARNET: patients with recurrent or advanced dMMR/MSI-H EC who have progressed on or

after treatment with a platinum-containing regimen
The efficacy and safety of dostarlimab as monotherapy were investigated in GARNET, a
multicentre, open-label, Phase 1 dose escalation study conducted in patients with recurrent
or advanced EC that has progressed on or after treatment with a platinum-containing
regimen.
The GARNET study included expansion cohorts in subjects with recurrent or advanced solid
tumours who have limited available treatment options. Cohort A1 enrolled patients with
mismatch repair deficient (dMMR) EC that has progressed on or after a platinum-containing
regimen.
Patients received dostarlimab 500 mg every 3 weeks for 4 cycles followed by 1,000 mg
every 6 weeks. Treatment continued until unacceptable toxicity or disease progression for up
to two years. The major efficacy outcome measures were objective response rate (ORR)
and duration of response (DOR) as assessed by blinded independent central radiologists’
(BICR) review according to RECIST v1.1. The secondary endpoints included disease control
rate (DCR) and PFS both assessed by BICR review according to RECIST v1.1; and OS.
All patients included in both the primary and secondary efficacy analysis set had a minimum
follow-up period of 24 weeks from first dose, regardless of whether they had a post-
treatment scan.
A total of 141 patients with dMMR EC were evaluated for efficacy in the GARNET study.
Among these 141 patients, the baseline characteristics were: median age 65.0 years (50%
age 65 or older); 76.6% White, 3.5% Asian, 2.8% Black; and Eastern Cooperative Oncology

22
Group (ECOG) PS 0 (38.3%) or 1 (61.7%). The median number of prior therapies for
recurrent or advanced endometrial cancer was one: 63% of patients had one prior line, 37%
had two or more prior lines. Forty-eight patients (34%) received treatment only in the
neoadjuvant or adjuvant setting before participating in the study.
The identification of dMMR/MSI-H tumour status was prospectively determined based on
local testing.
Local diagnostic assays (IHC, PCR or NGS) available at the sites were used for the
detection of the dMMR/MSI-H expression in tumour material. Most of the sites used IHC as it
was the most common assay available.
Efficacy results are shown in Table 9 and Figure 1.

Table 9. Efficacy results in GARNET for patients with dMMR endometrial cancer

Endpoint Dostarlimab
(N=141)a
Primary endpoints
Objective response rate (ORR)
ORR n (%) 64 (45.4)
(95% CI)
(37.0, 54.0)
Complete response rate, n (%) 22 (15.6)
Partial response rate, n (%) 42 (29.8)
b
Duration of response (DOR)
Median in months Not reached
Patients with duration ≥ 12 months, n (%) 51 (79.7)
Patients with duration ≥ 24 months, n (%) 28 (43.8)
Secondary endpoints
Progression free Survival (PFS)
Median in months (95% CI)c 5.6 (4.1, 16.6)
Number (%) of patients with event 83 (58.9)
Probability of PFS at 6-months, (95% CI)c 49.2% (40.6, 57.2)
Probability of PFS at 9-months, (95% CI)c 47.6% (39.0, 55.7)
c
Probability of PFS at 12-months, (95% CI) 46.0% (37.4, 54.1)
Overall Survival (OS)
Median in months Not reached
Number (%) of patients with event 55 (39.0)
d
Disease control rate (DCR)
DCR n (%) 86 (60.3)
(95% CI) (51.7, 68.4)
CI = Confidence interval

23
a Efficacy data with a median follow-up of 27.6 months (cut-off date 01 Nov 2021)
b For patients with a partial or complete response
c by Kaplan-Meier method
d includes patient with complete response, partial response and stable disease for at least 12 weeks

Figure 3. Kaplan-Meier Plot for Progression Free Survival per RECIST 1.1 - Based on
BICR Assessment (Primary Efficacy Analysis Set) in patients with dMMR EC (N = 141)

1.0 Censored
Probability of Progression Free Survival

0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
EC: dMMR Median (95% CI): 5.6 (4.1, 16.6)
0.0

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Time since start of study treatment (months)
Number of Subjects at Risk

EC: dMMR 141 124 80 64 63 58 54 52 51 45 40 39 34 32 25 23 20 18 15 11 10 7 6 4 2 0

Elderly patients
Of the 515 patients treated with dostarlimab monotherapy (IA1 GARNET population at time
of data cut-off 01 March 2020), 51% were under 65 years, 38% were 65 75 years, and 12%
were 75 years or older. Safety risks were not observed to be increased in older subjects
compared to younger subjects.
In the 72 patients with dMMR/MSI-H EC (IA1 population at time of data cut-off 01 March
2020) in the efficacy analysis, the ORR by BICR (95 % CI) was 43.2 % (27.1 %, 60.5 %) in
patients under 65 years and 48.6 % (31.4 %, 66.0 %) in patients 65 years and older.
In the 105 patients with dMMR/MSI-H EC (IA2 population at time of data cut-off 01 March
2020) in the efficacy analysis, the ORR by BICR (95 % CI) was 45.3 % (31.6 %, 59.6%) in
patients under 65 years and 44.2% (30.5 %, 58.7 %) in patients 65 years and older.

Paediatric population

The safety and efficacy of dostarlimab in children and adolescents below 18 years of age
have not been established.

5.2 Pharmacokinetic properties

The pharmacokinetics (PK) of dostarlimab was assessed as monotherapy and when

administered in combination with chemotherapy.

24
Dostarlimab PK as monotherapy or in combination with chemotherapy were characterised
using population PK analysis from 869 patients with various solid tumours, including
546 patients with EC. The PK of dostarlimab are approximately dose proportional. When
dosed at the recommended therapeutic dose for monotherapy (500 mg administered
intravenously every 3 weeks for 4 doses, followed by 1,000 mg every 6 weeks), or at the
recommended therapeutic dose for combination with chemotherapy (500 mg administered
intravenously every 3 weeks for 6 doses, followed by 1000 mg every 6 weeks), dostarlimab
shows an approximate two-fold accumulation (Cmin) , consistent with the terminal half-life.
The exposure of dostarlimab as monotherpay and/or in combination with chemotherapy was
similar.
Absorption

Dostarlimab is administered via the intravenous route and therefore estimates of absorption
are not applicable.
Distribution

The geometric mean volume of distribution of dostarlimab at steady state is approximately

5.81 L (CV% of 14.2%).
Biotransformation

Dostarlimab is a therapeutic mAb IgG4 that is expected to be catabolised into small

peptides, amino acids, and small carbohydrates by lysosome through fluid-phase or
receptor-mediated endocytosis. The degradation products are eliminated by renal excretion
or returned to the nutrient pool without biological effects.
Elimination

The geometric mean clearance is 0.00681 L/h (CV% of 30.2%) at steady state. The
geometric mean terminal half-life (t1/2) at steady state is 23.2 days (CV% of 20.8%).
Dostarlimab clearance was estimated to be 7.8% lower when dostarlimab was given in
combination with chemotherapy. There was no meaningful impact on dostarlimab exposure.
Linearity/non-linearity

Exposure (both maximum concentration [Cmax] and the area under the concentration-time
curve, [AUC0-tau] and [AUC0-inf]) was approximately dose proportional.

Special patient populations

A population PK analysis of the patient data indicates that there are no clinically important
effects of age (range: 24 to 86 years), sex or race, ethnicity, or tumour type on the clearance
of dostarlimab. This population PK model also indicates that alterations in renal function
(normal to moderate) and hepatic function (normal to mild impairment) do not alter the
disposition of dostarlimab.

5.3 Preclinical safety data

Genotoxicity
No studies have been performed to assess the potential of dostarlimab for genotoxicity.
Carcinogenicity
No studies have been performed to assess the potential of dostarlimab for carcinogenicity.

25
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients

Sodium citrate dihydrate

Citric acid monohydrate
Arginine hydrochloride
Sodium chloride
Polysorbate 80
Water for injection

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this
medicine.
6.3 Shelf life

36 months.

6.4 Special precautions for storage

Store in a refrigerator 2°C to 8°C.

Do not freeze.
Store in the original carton until time of preparation in order to protect from light. The
prepared dose may be stored either:
- At room temperature up to 25ºC for no more than 6 hours from the time of dilution
until the end of infusion.
- Under refrigeration at 2°C to 8°C for no more than 24 hours from time of dilution until
end of infusion. If refrigerated, allow the diluted solution to come to room temperature
prior to administration.

After preparation of infusion

To reduce microbiological hazard, use as soon as practicable after
reconstitution/preparation. If not used immediately, and infusion dilution was performed
aseptically, in-use chemical and physical stability have been demonstrated for up to 24
hours at 2°C to 8°C and up to 6 hours at room temperature (up to 25°C) from time of vial
puncture to the end of administration.
Due to the lack of preservative, the product must not be used beyond these storage times.
Product is for single use in one patient only, discard any residue.

26
6.5 Nature and contents of container and special equipment for use,
administration or implantation

10 mL Type I borosilicate clear glass vial, with a grey chlorobutyl elastomer stopper
laminated with fluoropolymer, sealed with an aluminium flip-off cap containing 500 mg
dostarlimab.

6.6 Special precautions for disposal

Any unused medicine or waste material should be disposed of by taking to your local
pharmacy.
Dilution
For the 500 mg dose, withdraw 10 mL of dostarlimab from a vial and transfer into an
intravenous (IV) bag containing sodium chloride 9 mg/mL (0.9%) solution for injection, or
glucose 50 mg/mL (5%) solution for injection. The final concentration of the diluted solution
should be between 2 mg/mL and 10 mg/mL. The total volume of the infusion solution must
not exceed 250 mL. This may require withdrawing a volume of diluent from the IV bag prior
to adding a volume of dostarlimab into the IV bag.

- For example, if preparing a 500 mg dose in a 250 mL diluent IV bag, to achieve a 2

mg/mL concentration would require withdrawing 10 mL of diluent from the 250 mL IV
bag. Then, 10 mL of dostarlimab would be withdrawn from the vial and transferred into
the IV bag.
For the 1,000 mg dose, withdraw 10 mL of dostarlimab from each of two vials (withdraw 20
mL total) and transfer into an IV bag containing sodium chloride 9 mg/mL (0.9%) solution for
injection or glucose 50 mg/mL (5%) solution for injection. The final concentration of the
diluted solution should be between 4 mg/mL and 10 mg/mL. The total volume of the infusion
solution must not exceed 250 mL. This may require withdrawing a volume of diluent from the
IV bag prior to adding a volume of dostarlimab into the IV bag.

- For example, if preparing a 1,000 mg dose in a 250 mL diluent IV bag, to achieve a 4

mg/mL concentration would require withdrawing 20 mL of diluent from the 250 mL IV
bag. Then, 10 mL of dostarlimab would be withdrawn from each of two vials, totaling
20 mL, and transferred into the IV bag.
Mix diluted solution by gentle inversion. Do not shake the final infusion bag. Discard any
unused portion left in the vial.

7. MEDICINE SCHEDULE
Prescription Medicine

8. SPONSOR
GlaxoSmithKline NZ Limited
Private Bag 106600
Downtown
Auckland
New Zealand

27
Phone: (09) 367 2900
Facsimile: (09) 367 2910

9. DATE OF FIRST APPROVAL

Date of publication in the New Zealand Gazette of consent to distribute the medicine: 6 July
2023

10. DATE OF REVISION OF THE TEXT

29 May 2024

Summary table of changes:

Section changed Summary of new information

Multiple Editorial amendments to enhance readability
Update to frequencies for adrenal insufficiency and
4.8
pancreatitis in combination therapy
6.6 Addition of maximum infusion volume

Version 4.0

Trade marks are owned by or licensed to the GSK group of companies.

© 2024 GSK group of companies or its licensor.

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