ASH News Daily 2017 - Issue 2 - A-16

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ALIQOPA™ (copanlisib) for injection, for intravenous use
Initial U.S. Approval: 2017
BRIEF SUMMARY OF PRESCRIBING INFORMATION
CONSULT PACKAGE INSERT FOR
FULL PRESCRIBING INFORMATION
1
INDICATIONS AND USAGE
ALIQOPA is indicated for the treatment of adult patients with relapsed follicular lymphoma (FL)
who have received at least two prior systemic therapies.
Accelerated approval was granted for this indication based on overall response rate [see Clinical
Studies (14.1)]. Continued approval for this indication may be contingent upon verification and
description of clinical benefit in a confirmatory trial.
4
None.

CONTRAINDICATIONS

6.1
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared to rates in the
clinical trials of another drug and may not reflect the rates observed in the general patient
population.
The safety data reflect exposure to ALIQOPA in 168 adults with follicular lymphoma and
other hematologic malignancies treated with ALIQOPA 60 mg or 0.8 mg/kg equivalent in
clinical trials. The median duration of treatment was 22 weeks (range 1 to 206 weeks).
Serious adverse reactions were reported in 44 (26%) patients. The most frequent
serious adverse reactions that occurred were pneumonia (8%), pneumonitis (5%) and
hyperglycemia (5%). The most common adverse reactions (≥20%) were hyperglycemia,
diarrhea, decreased general strength and energy, hypertension, leukopenia, neutropenia,
nausea, lower respiratory tract infections, and thrombocytopenia.
Adverse reactions resulted in dose reduction in 36 (21%) and discontinuation in 27
(16%) patients. The most common reasons for dose reduction were hyperglycemia
(7%), neutropenia (5%), and hypertension (5%). The most common reasons for drug
discontinuation were pneumonitis (2%) and hyperglycemia (2%).
Table 2 provides the adverse reactions occurring in at least 10% of patients receiving
ALIQOPA monotherapy, and Table 3 provides the treatment-emergent laboratory
abnormalities in ≥20% of patients and ≥4% of Grade ≥3 treated with ALIQOPA.
Table 2: Adverse Reactions Reported in ≥10% of Patients with Follicular Lymphoma and
Other Hematological Malignancies Treated with ALIQOPA
ADVERSE REACTIONS

90 (54%)

56 (33%)

10 (6%)

61 (36%)
53 (32%)
37 (22%)

20 (12%)
16 (10%)
12 (7%)

26 (15%)
26 (15%)
2 (1%)

61 (36%)

6 (4%)

0

60 (36%)
43 (26%)
24 (14%)
21 (13%)

8 (5%)
1 (<1%)
3 (2%)
0

0
0
0
0

59 (35%)

46 (27%)

0

35 (21%)

20 (12%)

3 (2%)

26 (15%)

2 (1%)

1 (<1%)

Additional adverse drug reactions reported at a frequency of <10% in patients with follicular
lymphoma and other hematologic malignancies include pneumonitis (9%), mucosal
inflammation (8%), and paresthesia and dysesthesia (7%).
Table 3: Treatment-emergent Laboratory Abnormalities in ≥20% of Patients and ≥4% of
Grade ≥3 Treated with ALIQOPA
Copanlisib Monotherapy N = 168*
Laboratory Parameter
Hematology abnormalities
Decreased hemoglobin
Lymphocyte count decreased
White blood cell decreased
Platelet count decreased
Neutrophil count decreased
Serum chemistry abnormalities
Hyperglycemia
Hypertriglyceridemia
Hypophosphatemia
Hyperuricemia
Serum lipase increased

Any Grade** Grade 3** Grade 4**
n (%)
n (%)
n (%)
130 (78%)
126 (78%)
118 (71%)
109 (65%)
104 (63%)

7 (4%)
43 (27%)
30 (18%)
11 (7%)
20 (12%)

0
4 (2%)
3 (2%)
3 (2%)
25 (15%)

160 (95%)
74 (58%)
72 (44%)
42 (25%)
34 (21%)

72 (43%)
6 (5%)
24 (15%)
40 (24%)
11 (7%)

9 (5%)
0
0
2 (1%)
2 (1%)

* Denominator for each laboratory parameter may vary based on number of patients with
specific numeric laboratory values available.
**NCI-CTCAE v4.03

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Metabolism and nutrition disorders
Hyperglycemia
Blood and lymphatic system disorders
Leukopenia
Neutropenia (including febrile neutropenia)
Thrombocytopenia
General disorders and administration site conditions
Decreased general strength and energy
(includes fatigue and asthenia)
Gastrointestinal disorders
Diarrhea
Nausea
Stomatitis (includes oropharyngeal erosion and ulcer, oral pain)
Vomiting
Vascular disorders
Hypertension (includes secondary hypertension)
Infections
Lower respiratory tract infections (includes pneumonia,
pneumonia bacterial, pneumonia pneumococcal, pneumonia
fungal, pneumonia viral, pneumocystis jiroveci pneumonia,
bronchopulmonary aspergillosis and lung infection)
Skin and subcutaneous tissue disorders
Rash (includes exfoliative skin reactions)

Copanlisib N = 168
Any Grade Grade 3
Grade 4
n (%)
n (%)
n (%)

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5
WARNINGS AND PRECAUTIONS
5.1
Infections
Serious, including fatal, infections occurred in 19% of 317 patients treated with ALIQOPA
monotherapy. The most common serious infection was pneumonia [see Adverse Reactions
(6.1)]. Monitor patients for signs and symptoms of infection and withhold ALIQOPA for Grade 3
and higher infection [see Dosage and Administration (2.5)].
Serious pneumocystis jiroveci pneumonia (PJP) occurred in 0.6% of 317 patients treated with
ALIQOPA monotherapy [see Adverse Reactions (6.1)]. Before initiating treatment with ALIQOPA,
consider PJP prophylaxis for populations at risk. Withhold ALIQOPA in patients with suspected
PJP infection of any grade. If confirmed, treat infection until resolution, then resume ALIQOPA at
previous dose with concomitant PJP prophylaxis [see Dosage and Administration (2.5)].
5.2
Hyperglycemia
Grade 3 or 4 hyperglycemia (blood glucose 250 mg/dL or greater) occurred in 41% of
317 patients treated with ALIQOPA monotherapy [see Adverse Reactions (6.1)]. Serious
hyperglycemic events occurred in 2.8% of patients. Treatment with ALIQOPA may result in
infusion-related hyperglycemia. Blood glucose levels typically peaked 5 to 8 hours post-infusion
and subsequently declined to baseline levels for a majority of patients; blood glucose levels
remained elevated in 17.7% of patients one day after ALIQOPA infusion. Of 155 patients with
baseline HbA1c <5.7%, 16 (10%) patients had HbA1c >6.5% at the end of treatment.
Of the twenty patients with diabetes mellitus treated in CHRONOS-1, seven developed Grade
4 hyperglycemia and two discontinued treatment. Patients with diabetes mellitus should only
be treated with ALIQOPA following adequate glucose control and should be monitored closely.
Achieve optimal blood glucose control before starting each ALIQOPA infusion. Withhold, reduce
dose, or discontinue ALIQOPA depending on the severity and persistence of hyperglycemia
[see Dosage and Administration (2.5)].
5.3
Hypertension
Grade 3 hypertension (systolic 160 mmHg or greater or diastolic 100 mmHg or greater)
occurred in 26% of 317 patients treated with ALIQOPA monotherapy [see Adverse Reactions
(6.1)]. Serious hypertensive events occurred in 0.9% of 317 patients. Treatment with ALIQOPA
may result in infusion-related hypertension. The mean change of systolic and diastolic BP from
baseline to 2 hours post-infusion on Cycle 1 Day 1 was 16.8 mmHg and 7.8 mmHg, respectively.
The mean BP started decreasing approximately 2 hours post-infusion; BP remained elevated
for 6 to 8 hours after the start of the ALIQOPA infusion. Optimal BP control should be achieved
before starting each ALIQOPA infusion. Monitor BP pre- and post-infusion. Withhold, reduce
dose, or discontinue ALIQOPA depending on the severity and persistence of hypertension [see
Dosage and Administration (2.5)].
5.4
Non-Infectious Pneumonitis
Non-infectious pneumonitis occurred in 5% of 317 patients treated with ALIQOPA monotherapy
[see Adverse Reactions (6.1)]. Withhold ALIQOPA and conduct a diagnostic examination of a
patient who is experiencing pulmonary symptoms such as cough, dyspnea, hypoxia, or interstitial
infiltrates on radiologic exam. Patients with pneumonitis thought to be caused by ALIQOPA
have been managed by withholding ALIQOPA and administration of systemic corticosteroids.
Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of
non-infectious pneumonitis [see Dosage and Administration (2.5)].
5.5
Neutropenia
Grade 3 or 4 neutropenia occurred in 24% of 317 patients treated with ALIQOPA monotherapy.
Serious neutropenic events occurred in 1.3% [see Adverse Reactions (6.1)]. Monitor blood
counts at least weekly during treatment with ALIQOPA. Withhold, reduce dose, or discontinue
ALIQOPA depending on the severity and persistence of neutropenia [see Dosage and
Administration (2.5)].
5.6
Severe Cutaneous Reactions
Grade 3 and 4 cutaneous reactions occurred in 2.8% and 0.6% of 317 patients treated with
ALIQOPA monotherapy, respectively [see Adverse Reactions (6.1)]. Serious cutaneous reaction
events were reported in 0.9%. The reported events included dermatitis exfoliative, exfoliative
rash, pruritus, and rash (including maculo-papular rash). Withhold, reduce dose, or discontinue
ALIQOPA depending on the severity and persistence of severe cutaneous reactions [see Dosage
and Administration (2.5)].
5.7
Embryo-Fetal Toxicity
Based on findings in animals and its mechanism of action, ALIQOPA can cause fetal harm when
administered to a pregnant woman. In animal reproduction studies, administration of copanlisib
to pregnant rats during organogenesis caused embryo-fetal death and fetal abnormalities in rats
at maternal doses as low as 0.75 mg/kg/day (4.5 mg/m2/day body surface area) corresponding
to approximately 12% the recommended dose for patients. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential and males with female partners of
reproductive potential to use effective contraception during treatment and for at least one month
after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].

6
ADVERSE REACTIONS
The following serious adverse reactions are described elsewhere in the labeling.
* Infections [see Warnings and Precautions (5.1)]
* Hyperglycemia [see Warnings and Precautions (5.2)]
* Hypertension [see Warnings and Precautions (5.3)]
* Non-infectious pneumonitis [see Warnings and Precautions (5.4)]
* Neutropenia [see Warnings and Precautions (5.5)]
* Severe cutaneous reactions [see Warnings and Precautions (5.6)]



Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 2

ASH News Daily 2017 - Issue 2 - A-1
ASH News Daily 2017 - Issue 2 - A-2
ASH News Daily 2017 - Issue 2 - A-3
ASH News Daily 2017 - Issue 2 - A-4
ASH News Daily 2017 - Issue 2 - A-5
ASH News Daily 2017 - Issue 2 - A-6
ASH News Daily 2017 - Issue 2 - A-7
ASH News Daily 2017 - Issue 2 - A-8
ASH News Daily 2017 - Issue 2 - A-9
ASH News Daily 2017 - Issue 2 - A-10
ASH News Daily 2017 - Issue 2 - A-11
ASH News Daily 2017 - Issue 2 - A-12
ASH News Daily 2017 - Issue 2 - A-13
ASH News Daily 2017 - Issue 2 - A-14
ASH News Daily 2017 - Issue 2 - A-15
ASH News Daily 2017 - Issue 2 - A-16
ASH News Daily 2017 - Issue 2 - A-17
ASH News Daily 2017 - Issue 2 - A-18
ASH News Daily 2017 - Issue 2 - A-19
ASH News Daily 2017 - Issue 2 - A-20
ASH News Daily 2017 - Issue 2 - A-21
ASH News Daily 2017 - Issue 2 - A-22
ASH News Daily 2017 - Issue 2 - A-23
ASH News Daily 2017 - Issue 2 - A-24
ASH News Daily 2017 - Issue 2 - A-25
ASH News Daily 2017 - Issue 2 - A-26
ASH News Daily 2017 - Issue 2 - A-27
ASH News Daily 2017 - Issue 2 - A-28
ASH News Daily 2017 - Issue 2 - B-1
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ASH News Daily 2017 - Issue 2 - B-3
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ASH News Daily 2017 - Issue 2 - B-53
ASH News Daily 2017 - Issue 2 - B-54
ASH News Daily 2017 - Issue 2 - B-55
ASH News Daily 2017 - Issue 2 - B-56
ASH News Daily 2017 - Issue 2 - C-1
ASH News Daily 2017 - Issue 2 - C-2
ASH News Daily 2017 - Issue 2 - C-3
ASH News Daily 2017 - Issue 2 - C-4
ASH News Daily 2017 - Issue 2 - C-5
ASH News Daily 2017 - Issue 2 - C-6
ASH News Daily 2017 - Issue 2 - C-7
ASH News Daily 2017 - Issue 2 - C-8
ASH News Daily 2017 - Issue 2 - C-9
ASH News Daily 2017 - Issue 2 - C-10
ASH News Daily 2017 - Issue 2 - C-11
ASH News Daily 2017 - Issue 2 - C-12
ASH News Daily 2017 - Issue 2 - C-13
ASH News Daily 2017 - Issue 2 - C-14
ASH News Daily 2017 - Issue 2 - C-15
ASH News Daily 2017 - Issue 2 - C-16
ASH News Daily 2017 - Issue 2 - C-17
ASH News Daily 2017 - Issue 2 - C-18
ASH News Daily 2017 - Issue 2 - C-19
ASH News Daily 2017 - Issue 2 - C-20
ASH News Daily 2017 - Issue 2 - C-21
ASH News Daily 2017 - Issue 2 - C-22
ASH News Daily 2017 - Issue 2 - C-23
ASH News Daily 2017 - Issue 2 - C-24
ASH News Daily 2017 - Issue 2 - C-25
ASH News Daily 2017 - Issue 2 - C-26
ASH News Daily 2017 - Issue 2 - C-27
ASH News Daily 2017 - Issue 2 - C-28
ASH News Daily 2017 - Issue 2 - C-29
ASH News Daily 2017 - Issue 2 - C-30
ASH News Daily 2017 - Issue 2 - C-31
ASH News Daily 2017 - Issue 2 - C-32
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