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POLIVY™ (polatuzumab vedotin-piiq) POLIVY™ (polatuzumab vedotin-piiq)
Safety was also evaluated in 173 adult patients with relapsed or refractory lymphoma who received
POLIVY, bendamustine, and either a rituximab product or obinutuzumab in Study GO29365, including
the 45 patients with DLBCL described above. In the expanded safety population, the median age was
66 years (range 27 – 86), 57% were male, 91% had an ECOG performance status of 0-1, and 32%
had a history of peripheral neuropathy at baseline.
Fatal adverse reactions occurred in 4.6% of recipients of POLIVY within 90 days of last treatment, with
infection as a leading cause. Serious adverse reactions occurred in 60%, most often from infection.
Table 5 summarizes the most common adverse reactions in the expanded safety population. The
overall safety profile was similar to that described above. Adverse reactions in ≥20% of patients
were diarrhea, neutropenia, peripheral neuropathy, fatigue, thrombocytopenia, pyrexia, decreased
appetite, anemia, and vomiting. Infection-related adverse reactions in >10% of patients included
upper respiratory tract infection, febrile neutropenia, pneumonia, and herpesvirus infection. 8.2 Lactation
Risk Summary
There is no information regarding the presence of polatuzumab vedotin-piiq in human milk, the effects
on the breastfed child, or milk production. Because of the potential for serious adverse reactions in
breastfed children, advise women not to breastfeed during treatment with POLIVY and for at least
2 months after the last dose.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
Verify pregnancy status in females of reproductive potential prior to initiating POLIVY [see Use in
Specific Populations (8.1)].
Contraception
Females
POLIVY can cause embryo-fetal harm when administered to pregnant women [see Use in Specific
Populations (8.1)]. Advise females of reproductive potential to use effective contraception during
treatment with POLIVY and for 3 months after the final dose [see Nonclinical Toxicology (13.1)].
Males
Based on genotoxicity findings, advise males with female partners of reproductive potential to use
effective contraception during treatment with POLIVY and for at least 5 months after the final dose [see
Nonclinical Toxicity (13.1)].
Infertility
Based on findings from animal studies, POLIVY may impair male fertility. The reversibility of this
effect is unknown [see Nonclinical Toxicology (13.1)].
8.4 Pediatric Use
Safety and effectiveness of POLIVY have not been established in pediatric patients.
8.5 Geriatric Use
Among 173 patients treated with POLIVY in Study GO29365, 95 (55%) were ≥65 years of age.
Patients aged ≥65 had a numerically higher incidence of serious adverse reactions (64%) than
patients aged <65 (53%). Clinical studies of POLIVY did not include sufficient numbers of patients
aged ≥65 to determine whether they respond differently from younger patients.
8.6 Hepatic Impairment
Avoid the administration of POLIVY in patients with moderate or severe hepatic impairment (bilirubin
greater than 1.5 × ULN). Patients with moderate or severe hepatic impairment are likely to have
increased exposure to MMAE, which may increase the risk of adverse reactions. POLIVY has not
been studied in patients with moderate or severe hepatic impairment [see Clinical Pharmacology
(12.3) and Warnings and Precautions (5.7)].
No adjustment in the starting dose is required when administering POLIVY to patients with mild hepatic
impairment (bilirubin greater than ULN to less than or equal to 1.5 × ULN or AST greater than ULN).
17 PATIENT COUNSELING INFORMATION
Peripheral Neuropathy
Advise patients that POLIVY can cause peripheral neuropathy. Advise patients to report to their
healthcare provider any numbness or tingling of the hands or feet or any muscle weakness [see
Warnings and Precautions (5.1)].
Infusion-Related Reactions
Advise patients to contact their healthcare provider if they experience signs and symptoms of
infusion reactions, including fever, chills, rash or breathing problems within 24 hours of infusion [see
Warnings and Precautions (5.2].
Myelosuppression
Advise patients to report signs or symptoms of bleeding or infection immediately. Advise patients of
the need for periodic monitoring of blood counts [see Warnings and Precautions (5.3)].
Infections
Advise patients to contact their healthcare provider if a fever of 38°C (100.4°F) or greater or other
evidence of potential infection such as chills, cough, or pain on urination develops. Advise patients of
the need for periodic monitoring of blood counts [see Warnings and Precautions (5.4)].
Progressive Multifocal Leukoencephalopathy
Advise patients to seek immediate medical attention for new or changes in neurological symptoms
such as confusion, dizziness, or loss of balance; difficulty talking or walking; or changes in vision
[see Warnings and Precautions (5.5)].
Tumor Lysis Syndrome
Advise patients to seek immediate medical attention for symptoms of tumor lysis syndrome such as
nausea, vomiting, diarrhea, and lethargy [see Warnings and Precautions (5.6)].
Hepatotoxicity
Advise patients to report symptoms that may indicate liver injury, including fatigue, anorexia, right
upper abdominal discomfort, dark urine, or jaundice [see Warnings and Precautions (5.7)].
Embryo-Fetal Toxicity
Advise females of reproductive potential of the potential risk to a fetus. Advise females to contact
their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment
with POLIVY [see Warnings and Precautions (5.8) and Use in Specific Populations (8.1)].
Females and Males of Reproductive Potential
Advise females of reproductive potential, and males with female partners of reproductive potential,
to use effective contraception during treatment with POLIVY and for at least 3 months and 5 months
after the last dose, respectively [see Use in Specific Populations (8.3)].
Lactation
Advise women not to breastfeed while receiving POLIVY and for at least 2 months after the last dose
[see Use in Specific Populations (8.2)].
Table 5 Most Common Adverse Reactions (≥20% Any Grade or ≥5% Grade 3 or Higher) in
Recipients of POLIVY and Chemoimmunotherapy for Relapsed or Refractory Lymphoma
Adverse Reaction by Body System
POLIVY + Bendamustine + Rituximab
Product or Obinutuzumab
n = 173
All Grades,
(%)
Grade 3 or Higher,
(%)
Blood and Lymphatic System Disorders
Neutropenia
44
39
Thrombocytopenia
31
23
Anemia
28
14
Febrile neutropenia a
13
13
Leukopenia
13
8
Lymphopenia
12
12
Nervous System Disorders
Peripheral neuropathy
40
2.3
Gastrointestinal Disorders
Diarrhea
45
8
Vomiting
27
2.9
General Disorders
Fatigue
40
5
Pyrexia
30
2.9
Decreased appetite
29
1.7
Infections
Pneumonia
13
10 b
Sepsis
6
6 c
Metabolism and Nutrition Disorders
Hypokalemia
18
6
The table includes a combination of grouped and ungrouped terms.
a
Primary prophylaxis with granulocyte colony-stimulating factor was given to 46% of all patients.
b
Includes 5 events with fatal outcome. c Includes 4 events with fatal outcome.
Other clinically relevant adverse reactions (<20% any grade) included: General disorders: infusion-
related reaction (7%), Infection: upper respiratory tract infection (16%), lower respiratory tract
infection (10%), herpes virus infection (12%), cytomegalovirus infection (1.2%), Respiratory:
dyspnea (19%), pneumonitis (1.7%), Nervous system disorders: dizziness (10%), Investigations:
weight decrease (10%), transaminase elevation (8%), lipase increase (3.5%), Musculoskeletal
disorders: arthralgia (7%), Eye disorders: blurred vision (1.2%)
6.2 Immunogenicity
As with all therapeutic proteins, there is a 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 neutralizing 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 these reasons, comparison of
the incidence of antibodies to polatuzumab vedotin-piiq in the studies described below with the
incidence of antibodies in other studies or to other products may be misleading.
Across all arms of Study GO29365, 8/134 (6%) patients tested positive for antibodies against
polatuzumab vedotin-piiq at one or more post-baseline time points. Across clinical trials, 14/536
(2.6%) evaluable POLIVY-treated patients tested positive for such antibodies at one or more post-
baseline time points. Due to the limited number of patients with antibodies against polatuzumab
vedotin-piiq, no conclusions can be drawn concerning a potential effect of immunogenicity on
efficacy or safety.
7 DRUG INTERACTIONS
7.1 Effects of Other Drugs on POLIVY
Strong CYP3A Inhibitors
Concomitant use with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC [see Clinical
Pharmacology (12.3)], which may increase POLIVY toxicities. Monitor patients for signs of toxicity.
Strong CYP3A Inducers
Concomitant use with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC [see Clinical
Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology
(12.1)], POLIVY can cause fetal harm. There are no available data in pregnant women to inform
the drug-associated risk. In animal reproduction studies, administration of the small molecule
component of POLIVY, MMAE, to pregnant rats during organogenesis at exposures below the clinical
exposure at the recommended dose of 1.8 mg/kg POLIVY every 21 days resulted in embryo-fetal
mortality and structural abnormalities (see Data). Advise a pregnant woman of the potential risks
to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is
unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage
in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Data
Animal Data
No embryo-fetal development studies in animals have been performed with polatuzumab vedotin-
piiq. In an embryo-fetal developmental study in pregnant rats, administration of two intravenous
doses of MMAE, the small molecule component of POLIVY, on gestational days 6 and 13 caused
embryo-fetal mortality and structural abnormalities, including protruding tongue, malrotated limbs,
gastroschisis, and agnathia compared to controls at a dose of 0.2 mg/kg (approximately 0.5-fold the
human area under the curve [AUC] at the recommended dose).
POLIVY™ (polatuzumab vedotin-piiq)
Manufactured by:
Genentech, Inc.
A Member of the Roche Group
1 DNA Way
South San Francisco, CA
94080-4990
M-US-00000111 (v1.0) 09/19
Initial U.S. Approval:
June 2019
POLIVY ™ is a trademark
of Genentech, Inc.
© 2019 Genentech, Inc.