What is tisotumab vedotin? Tisotumab vedotin-tftv (Tivdak) is an intravenous (IV) infusion, combining a tissue factor-directed antibody and a microtubule-disrupting agent. The tisotumab antibody portion is a human IgG1 directed against cell surface TF, found to be highly prevalent in cervical cancer tissue. The small molecule, monomethyl auristatin E (MMAE), is a microtubule-disrupting agent, attached to the antibody via a protease-cleavable linker. Tisotumab vedotin works by binding to TF expressed on cancer cells, forming a complex that is subsequently internalized into the cell. Proteolytic enzymes release MMAE, which disrupts the microtubule network of dividing cells, leading to cell cycle arrest and apoptosis. What is this approved for? Tisotumab vedotin is approved for adult patients with recurrent or metastatic cervical cancer with disease progression during or after standard chemotherapy with platinum + paclitaxel ± bevacizumab. Approval was based on innovaTV 204, a multicenter, single-arm, Phase II clinical trial. Efficacy and safety were evaluated in patients (n=101) with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based regimen. More than 70 percent of patients received tisotumab vedotin in the second-line setting. The main efficacy outcome measures of innovaTV 204 were objective response rate (ORR) and duration of response (DOR). The ORR was 24 percent with a median DOR of 8.3 months. Median progression free survival was 4.2 months and median overall survival was 12.1 months, leading to accelerated FDA approval in September 2021. How do you administer this drug? Tisotumab vedotin is administered via IV infusion over 30 minutes, once every 3 weeks. Dosing is 2 mg/kg (200 mg maximum). Are there any premedications needed for tisotumab vedotin? Patients should receive one corticosteroid drop per eye and three vasoconstrictor drops per eye, 10 minutes prior to each infusion. Cold packs should be placed over the eyes starting approximately 10 minutes prior to infusion and kept on until 20 minutes after completion. Patients should also receive an antiemetic premedication, given low-emetic risk. What are common side effects (≥10%)? Gastrointestinal: nausea (41%), diarrhea (25%), constipation (23%), abdominal pain (23%), vomiting (17%), reduced appetite (16%) Dermatologic: alopecia (39%), rash (25%), pruritis (13%) Vascular: epistaxis (39%), hemorrhage (32%) Ophthalmic: conjunctival adverse reactions (37%), dry eye (29%), corneal adverse reactions (21%), periorbital adverse reactions (16%) Neuromuscular/skeletal: fatigue (50%), myalgias (21%), arthralgias (16%), peripheral neuropathy (39%) Infection: urinary tract infection (14%) Miscellaneous: pyrexia (16%), weight loss (12%) Increased lab values: creatinine (29%), prothrombin international normalized ratio (26%), activated partial thromboplastin time (26%), alanine aminotransferase (24%), lactate dehydrogenase (22%), urate (20%), aspartate aminotransferase (AST) (18%), alkaline phosphatase (17%), creatinine kinase (16%) Decreased lab values: hemoglobin (52%), lymphocytes (42%), leukocytes (30%), neutrophils (21%), glucose (19%), sodium (20%), magnesium (17%), albumin (16%) What are the uncommon side effects (5-10%)? Cardiovascular: pulmonary embolism (3%), venous thrombosis (3%) Gastrointestinal: intestinal obstruction (6%) Genitourinary: hematuria (10%), vaginal hemorrhage (10%) Immunologic: antibody development (5-6%) Infection: sepsis (3%) Nervous system: myasthenia (3%), peripheral demyelinating polyneuropathy (1%), peripheral motor neuropathy (3%), sensorimotor neuropathy (5%) Ophthalmic: decreased visual acuity (5%) Respiratory: pneumonia (4%), pneumonitis (2%) Are there any important drug interactions I should be aware of? The MMAE component of tisotumab vedotin is a major CYP3A4 substrate. Avoid concurrent administration with strong CYP3A4 inhibitors. How do I adjust the dose in the setting of renal or hepatic insufficiency? There are no recommended dose adjustments for creatinine clearance <30 mL/min or end-stage renal disease due to lack of data. For moderate to severe hepatic impairment with AST >3 times upper limit of normal (ULN) and/or total bilirubin >1.5 times ULN, avoid tisotumab vedotin use. What should my patients know about tisotumab vedotin? Important counseling points include ocular toxicities (see below), peripheral neuropathy, fatigue, bleeding (mostly epistaxis), reduced blood cell counts and secondary risk of infection, and alopecia. Mitigation of ocular toxicity: Referral to ophthalmologist for a baseline evaluation and follow-up exams before each infusion Avoid wearing contact lenses Cold packs will be applied over the eyes before, during, and after infusions Required eye drop prescriptions: Corticosteroid drops: Administer 1 drop in each eye 10 minutes prior to tisotumab vedotin; then 1 drop in each eye 3 times daily for 72 hours after infusions Vasoconstrictor drops: Administer 3 drops in each eye 10 minutes prior to infusions Lubricating drops: use as needed for eye irritation throughout treatment and for 30 days after the last tisotumab vedotin treatment What useful links are available regarding tisotumab vedotin? FDA Accelerated Approval: https://bit.ly/3uowo3Z Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/ GOG-3023/ ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol 2021; doi: 10.1016/S1470-2045(21)00056-5 Eye Care: https://www.tivdak.com/caring-for-your-eyes/ Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-inhuman, multicentre, phase 1-2 trial. Lancet Oncol 2019; doi: 10.1016/S1470-2045(18)30859-3. Any ongoing clinical trials related to tisotumab vedotin? A trial comparing tisotumab vedotin to chemotherapy in recurrent or metastatic cervical cancer is ongoing, as well as a study assessing safety and efficacy of tisotumab vedotin in other solid tumors, such as colorectal and lung cancer. Another ongoing trial in cervical cancer is assessing combination therapy of tisotumab vedotin with bevacizumab, pembrolizumab, or carboplatin. More information is available about these trials at clinicaltrials.gov. CASSANDRA PERKEY, PHARMD, BCOP, is an Oncology Clinical Pharmacist at UK HealthCare, Markey Cancer Center in Lexington, KY. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/Manager, Clinical Pharmacy Services at Washington University School of Medicine. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.Cassandra Perkey, PharmD, BCOP: Cassandra Perkey, PharmD, BCOPJanelle E. Mann, PharmD, BCOP: Janelle E. Mann, PharmD, BCOPRamaswamy Govindan, MD: Ramaswamy Govindan, MD