Tisotumab vedotin-tftv

Common name: Tisotumab vedotin-tftv

Trade name: Tivdak

Full name: Tisotumab vedotin-tftv, Tivdak

Indications:

Treatment of recurrent and/or metastatic cervical cancer, ovarian cancer and other solid tumors

Usage and dosage:

The recommended dose is 2 mg/kg (the maximum dose is 200 mg), administered by intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.

The medical staff determines the patient’s infusion dose. During each infusion, medical staff will apply an ice pack to the patient's eyes.

If side effects occur, medical staff may reduce the infusion dose, suspend treatment, or stop treatment entirely.

Specification:

40mg/vial

Adverse reactions:

Peripheral neuropathy: You may feel numbness, tingling, and muscle weakness in your hands and feet

Bleeding: Signs or symptoms of bleeding may occur during treatment, such as blood in the stool or black stool (looking like tar), blood in the urine, coughing or vomiting blood, unusual vaginal bleeding, any unusual or heavy bleeding

Lung problems: Severe or life-threatening inflammation of the lungs may occur, leading to death. New or worsening symptoms may occur, including difficulty breathing, shortness of breath, or cough.

Common adverse reactions: decreased red and white blood cell counts, fatigue, nausea, hair loss, nosebleeds, changes in blood tests of kidney function, dry eye syndrome, abnormal coagulation test results, diarrhea, rash

Contraindications:

Precautions:

Eye problems: Tivdak can cause changes in the surface of the eyes that can lead to dry eyes, red eyes, eye irritation, corneal ulcers, blurred vision and severe vision loss. If you develop new or worsening vision changes or eye problems during treatment, inform your healthcare provider promptly.

Steroid eye drops should be used as prescribed before each infusion and 72 hours after the infusion.

Use vasoconstrictor eye drops before each infusion.

Use lubricating eye drops throughout treatment and for 30 days after the last dose.

Do not wear contact lenses during the entire treatment unless told to do so by your eye specialist.

Mechanism of action:

Tisotumab vedotin is an investigational ADC drug targeting tissue factor (TF). The drug is designed to target the TF antigen on cancer cells and deliver the cytotoxic agent MMAE (monomethyl auristatin E) directly into the cancer cells. In cancer biology, TF is a protein involved in tumor signaling and angiogenesis that is overexpressed in the vast majority of cervical cancer patients and many other solid tumors, including ovarian, lung, pancreatic, colorectal, and head and neck cancers. Based on the high expression and rapid internalization of TF factors in many solid tumors, TF has become an ideal target for the development of ADC drugs.

Safety and Efficacy:

The innovaTV 204 trial (also known as GCT1015-04 or GOG-3023/ENGOT-cx6) is an ongoing, single-arm, global, multicenter study in patients with recurrent or metastatic cervical cancer who have previously received dual chemotherapy with or without bevacizumab. Additionally, patients were eligible if they had received up to two prior lines of therapy in the recurrent or metastatic setting. In the study, 101 patients were treated with tisotumab vedotin at multiple centers in the United States and Europe. The primary endpoint of the trial is confirmed objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by independent entity review. Key secondary endpoints include duration of response, progression-free survival, overall survival, safety and tolerability.

The trial results showed that the objective response rate (ORR) confirmed by an independent central review was 24% [95% confidence interval (CI): 15.9%-33.3%], of which 7 cases (7%) had a complete response and 17 cases (17%) had a partial response. After a median follow-up of 10 months, the median duration of response (DOR) was 8.3 months (95% CI: 4.2, not reached). Study results also showed that the median time to response was 1.4 months (range, 1.1-5.1), with activity generally observed within the first two treatment cycles. Subgroup analysis showed that regardless of tumor histology, previous treatment routes, previous responses to systemic regimens, and dual chemotherapy with bevacizumab as first-line treatment, the responses were basically consistent between subgroups. Overall, the median PFS was 4.2 months (95% CI: 3.0, 4.4), the 6-month PFS rate was 30% (95% CI: 20.8, 40.1), the median OS was 12.1 months (95% CI: 9.6, 13.9), and the 6-month OS rate was 79% (95% CI: 69.3, 85.6).