Vusolimogene oderparepvec

Risk Summary

There are no available data with vusolimogene oderparepvec 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 vusolimogene oderparepvec, 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 vusolimogene oderparepvec, and 90 days after the last dose of vusolimogene oderparepvec.

Animal Data

In an embryofetal development study in pregnant rats, vusolimogene oderparepvec 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 vusolimogene oderparepvec, adverse maternal findings, or treatment-related effects on embryo-fetal development.

There are no data available on the presence of vusolimogene oderparepvec 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 vusolimogene oderparepvec and any potential adverse effects on the breastfed child from vusolimogene oderparepvec or from the underlying maternal condition.

No studies have been conducted with vusolimogene oderparepvec to assess its mutagenic or carcinogenic potential or effects on male fertility.

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 vusolimogene oderparepvec administered with nivolumab in 140 patients evaluated in the IGNYTE Study.

Patients received a median of 8 doses (range 1 to 32) of vusolimogene oderparepvec, and 7 (range 0 to 29) doses of nivolumab during the study. The median duration of the first course of vusolimogene oderparepvec 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.