TUDRIQEV Suspension for injection Ref.[116925] Active ingredients: Vusolimogene oderparepvec

5.1 Accidental Exposure

Accidental exposure of TUDRIQEV to close contacts may lead to transmission of herpetic infection. Healthcare providers, caregivers, close contacts, pregnant women, newborns, and patients should avoid direct contact with injected tumors, dressings, or bodily fluids of patients [see Use in Specific Populations (8.1)].

Healthcare providers and caregivers must wear protective gloves when applying or changing dressings and dispose of used dressings, gloves, and cleaning materials as biohazardous waste [see Dosage and Administration (2.2)].

If an accidental exposure to TUDRIQEV occurs (e.g. touching or scratching the unprotected injection site or dressings), exposed individuals should clean the affected area with soap and water. If signs and symptoms of herpetic infection develop, exposed individuals should contact their healthcare provider for assessment and treatment as clinically warranted.

5.2 Herpetic Infection or Reactivation

There is a potential risk for herpetic infection or reactivation after TUDRIQEV administration. Patients with suspected herpetic infections should contact their healthcare provider for assessment and antiviral treatment of the suspected herpetic infection as clinically warranted.

5.3 Injection Procedure Complications

Complications related to injection procedure have occurred, including but not limited to hemorrhage, infection, and visceral injury (for example: pneumothorax) [see Adverse Reaction (6.1)]. Monitor patients for signs and symptoms of visceral injury during and after TUDRIQEV administration and manage according to clinical practice.

5.4 Immune-Mediated Events

TUDRIQEV in combination with nivolumab may result in immune-mediated events. In clinical studies, immune-mediated events, including colitis, hepatitis, myocarditis, neuropathy, capillary leak syndrome, dermatitis, and vitiligo have been reported in patients treated with TUDRIQEV and nivolumab [see Adverse Reaction (6.1)].

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 practice.

The safety data described in this section reflect exposure of TUDRIQEV administered with nivolumab in 140 patients evaluated in the IGNYTE Study [see Clinical Studies (14)].

Patients received a median of 8 doses (range 1 to 32) of TUDRIQEV, and 7 (range 0 to 29) doses of nivolumab during the study. The median duration of the first course of TUDRIQEV and nivolumab exposure was 3.3 months (range 0.5 to 5.1 months) and 3.2 months (range 0 to 24.4 months), respectively.

Serious adverse reactions occurring in >1% patients include pleural effusion (n=3), acute kidney injury (n=2), arthralgia (n=2), atrial fibrillation (n=2), atrial flutter (n=2), cancer pain (n=2), hypophysitis (n=2), immune-mediated enterocolitis (n=2), pyrexia (n=2), sepsis (n=2), urinary tract infection (n=2), and myocardial infarction (n=2). Serious adverse reactions leading to death include myocardial infarction (n=1) and multiple organ dysfunction (n=1). Adverse reactions leading to discontinuation of treatment occurred in 22 (16%) patients.

Table 1 summarizes the most common adverse reactions that occurred in ≥10% patients in the IGNYTE Study.

Table 1. Adverse Reactions Occurring in ≥10% of Patients in IGNYTE Study (N=140):

^* Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. None of the common adverse reactions were Grade 4 or 5
^† a composite that includes multiple related terms

Other clinically significant adverse reactions occurring less than 10% include visceral injury including pneumothorax (n=3), oral herpes (n=2), herpes simplex (n=1), and herpes simplex reactivation (n=1).

Table 2 presents the most common laboratory abnormalities that worsened from baseline in ≥10% of patients in the IGNYTE Study.

Table 2. Laboratory Values Worsening from Baseline in ≥10% in IGNYTE (N=140):

^* Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

7.1 Effects of Antivirals

Antiviral medications may reduce the efficacy of TUDRIQEV. Patients receiving systemic antiviral treatment for herpetic infection should delay TUDRIQEV treatment for 72 hours after completion of antiviral therapy.

Risk Summary

There are no available data with TUDRIQEV in pregnant women to inform a drug-associated risk.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

If the patient becomes pregnant during treatment with TUDRIQEV, the patient should be apprised that there may be potential hazards to the fetus and neonate. Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy during treatment with TUDRIQEV, and 90 days after the last dose of TUDRIQEV.

Animal Data

In an embryofetal development study in pregnant rats, TUDRIQEV was intravenously administered at 5x10⁶ (5 million) PFU per kg once every three days during fetal organogenesis (gestational days 4 through 16) and was not associated with placental transfer of TUDRIQEV, adverse maternal findings, or treatment-related effects on embryo-fetal development.

Risk Summary

There are no data available on the presence of TUDRIQEV in human milk, the effects on the breastfed infant, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TUDRIQEV and any potential adverse effects on the breastfed child from TUDRIQEV or from the underlying maternal condition.

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating TUDRIQEV [see Use in Specific Populations (8.1)].

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with TUDRIQEV and for 90 days after the last dose [see Use in Specific Populations (8.1)].

Males

Advise males with a female partner of reproductive potential to use effective contraception, and to refrain from donating sperm during treatment with TUDRIQEV and for 90 days after the last dose [see Use in Specific Populations (8.1)].

Infertility

Females and Males

No nonclinical or clinical studies were performed to evaluate the effect of TUDRIQEV on fertility.

Safety and efficacy of TUDRIQEV have not been established in pediatric patients.

In the IGNYTE Study, 57 out of 140 patients (41%) were 65 years of age or older, and 20 (14%) were 75 years of age and older. No overall difference in safety or effectiveness was observed in patients over 65 years of age, including patients over 75 years of age, when compared with younger adult patients.