rvous 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 ofantibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity inan 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 describedbelow 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 againstpolatuzumab vedotin-piiq at one or more post-baseline time points. Across clinical trials,14/536 (2.6%) eva luable POLIVY-treated patients tested positive for such antibodies at one ormore post-baseline time points. Due to the limited number of patients with antibodies againstpolatuzumab vedotin-piiq, no conclusions can be drawn concerning a potential effect ofimmunogenicity 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 [seeClinical Pharmacology (12.3)], which may increase POLIVY toxicities. Monitor patients forsigns of toxicity.
Strong CYP3A Inducers
Concomitant use with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC [seeClinical 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 informthe drug-associated risk. In animal reproduction studies, administration of the small moleculecomponent of POLIVY, MMAE, to pregnant rats during organogenesis at exposures below theclinical exposure at the recommended dose of 1.8 mg/kg POLIVY every 21 days resulted inembryo-fetal mortality and structural abnormalities (see Data). Advise a pregnant woman of thepotential risks to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicatedpopulation is unknown. All pregnancies have a background risk of birth defect, loss, or otheradverse outcomes. In the U.S. general population, the estimated background risk of major birthdefects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
DataAnimal Data
No embryo-fetal development studies in animals have been performed with polatuzumabvedotin-piiq. In an embryo-fetal developmental study in pregnant rats, administration of twointravenous doses of MMAE, the small molecule component of POLIVY, on gestational days 6and 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).
8.2 Lactation
Risk Summary
There is no |
