FDA Approves Tivdak - First Tissue Factor (TF)-Targeted Antibody Conjugate Drug (ADC)

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FDA Approves Tivdak - First Tissue Factor
(TF)-Targeted Antibody Conjugate Drug (ADC)

Seagen and Genmab A/S jointly announced recently that the U.S. Food and Drug
Administration (FDA) has granted accelerated approval for the antibody conjugate drug
(ADC) Tivdak (tisotumab vedotin-tftv) for the treatment of adult patients with
recurrent or metastatic cervical cancer whose disease has progressed during or
after chemotherapy. It is the twelfth ADC approved by FDA. The approval is based on
tumor remission and remission persistence data, and subsequent full approval for this
indication will depend on the validation and characterization of the clinical benefit in
confirmatory clinical trials.

Tivdak will provide a new monotherapy option for women with recurrent or metastatic
cervical cancer who have progressed after first-line chemotherapy and for whom there are
limited treatment options available.

Tivdak is a first-in-class ADC targeting tissue factor (TF), a cell surface protein
expressed on a variety of solid tumors, including cervical cancer, that is associated with
tumor growth, angiogenesis, metastasis, and poor prognosis. Patients with previously
treated recurrent and/or metastatic cervical cancer typically exhibit very limited objective
remission rates to standard therapies, typically less than 15%, with a median overall
survival (OS) of only 6.0-9.4 months.

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This approval is based on the results of the pivotal Phase II innovaTV 204 study. The data
were presented at the European Society for Medical Oncology (ESMO) Virtual Congress
in September 2020. The results showed significant efficacy of Tivdak as a monotherapy,
providing clinically meaningful and durable objective remissions: an overall remission rate
(ORR) of 24%, median duration of remission (DOR) of 8.3 months, and a manageable
safety profile.

innovaTV 204 is an ongoing, single-arm, global, multicenter study in 101 patients with
recurrent or metastatic cervical cancer who have received prior dual chemotherapy (with
or without bevacizumab) but whose disease progressed, or who have received at least 2
therapies (including at least one platinum-containing chemotherapy) for recurrent and/or
metastatic disease. The study evaluated the efficacy and safety of Tivdak (administered
every 3 weeks). The primary endpoint was the objective remission rate (ORR) as
assessed by a blinded independent center review (BICR), with key secondary endpoints
including duration of remission (DOR), progression-free survival (PFS), overall survival
(OS), safety and tolerability.

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The results showed that the ORR of Tivdak treatment was 24% (95% CI:15.9-33.3%), with
a complete remission rate (CR) of 7% (7 cases) and a partial remission rate (PR) of 17%
(17 cases). The median follow-up was 10 months or with a median DOR of 8.3 months
(95% CI:4.2-not reached). The median time from initiation of treatment to remission was
1.4 months (range: 1.1-5.1), and treatment response was generally observed within the
first 2 treatment cycles. Subgroup analysis showed that remission rates were generally
consistent between subgroups, regardless of tumor histology, number of prior therapies
received, response to prior systemic regimens, and dual chemotherapy combined with
bevacizumab as first-line therapy.

The median PFS was 4.2 months (95% CI:3.0-4.4) and 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) as well as a 6-month
OS rate of 79% (95% CI:69.3-85.6). The most common treatment-related adverse events
(≥20%) in the study included alopecia, rhinorrhea, nausea, conjunctivitis, fatigue, and dry
eye.

These results confirm that Tivdak induces clinically meaningful and durable remissions
with a controlled and tolerable safety profile in patients with this difficult-to-treat cervical
cancer. The approval of Tivdak for marketing is a major step forward for women with
recurrent or metastatic cervical cancer.

​ Mechanism of action of tisotumab vedotin (image source: immunopaedia.org.za)

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Cervical cancer originates in the cells of the cervix, and the disease remains one of the
leading causes of cancer death in women worldwide, killing more than 311,000 women
each year, the vast majority of them in developing countries. In developed countries,
routine medical checkups and human papillomavirus (HPV) vaccination have reduced the
incidence of cervical cancer. Despite these advances, many women are still diagnosed
with cervical cancer that frequently recurs or metastasizes and can have devastating
effects.

Tivdak's active pharmaceutical ingredient is tisotumab vedotin, an ADC drug that targets
tissue factor (TF), combining Genmab's TF-targeting monoclonal antibody tisotumab with
Seattle Genetics' ADC technology, which is designed to target TF antigens on cancer
cells and deliver the cytotoxic agent MMAE ( monomethyl auristatin E) directly into cancer
cells. In cancer biology, TF is a protein involved in tumor signaling and angiogenesis and
is overexpressed in the vast majority of patients with cervical cancer and in 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 is an ideal target for the development of ADC drugs.

Tivdak is currently being developed jointly by Seattle Genetics and Genmab as a
monotherapy or in combination with other therapies for the treatment of recurrent and/or
metastatic cervical cancer, ovarian cancer and other solid tumors. In addition, they are
also evaluating the drug for weekly or 3-weekly dosing regimens.

Biochempeg, as a professional PEG derivatives supplier, is dedicated to being your most
reliable partner to provide chemical synthesis and high-quality PEG linkers. We are
committed to promoting the progress of your ADC discovery and development projects.

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Reference:
Seagen and Genmab Announce FDA Accelerated Approval for TIVDAK™° (tisotumab
vedotin-tftv) in Previously Treated Recurrent or Metastatic Cervical Cancer

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