Zai Lab, a patient focused, global biopharma company committed to driving the next wave of healthcare innovation confirmed that it had signed an exclusive collaboration and license agreement with Seagen for the development and commercialization of tisotumab vedotin (Tivdak®; Seagen/Genmab) in mainland China, Hong Kong, Macau, and Taiwan.

Tisotumab vedotin is the first and only antibody-drug conjugate or ADC approved in the United States for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

The drug is composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody.

Nonclinical data suggests that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

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Agreement
Under the terms of the agreement, Seagen will receive an upfront payment of US $ 30 million, as well as development, regulatory, and commercial milestone payments, and tiered royalties on net sales of tisotumab vedotin in the Zai Lab territory. Based on the existing tisotumab vedotin co-development and co-commercialization collaboration between Seagen and Genmab, all upfront, milestone payments, and royalties will be shared 50/50 with Genmab.

Approval
In 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval for tisotumab vedotin for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. As verification and description of clinical benefit in the U.S., and to support further global regulatory applications, a confirmatory phase 3 open-label, randomized, global clinical trial, innovaTV 301, is ongoing.

“This agreement enables us to leverage Zai Lab’s strong expertise in developing and commercializing innovative medicines in the licensed territory,” noted Natasha Hernday, EVP Corporate Development and Alliance Management, Seagen.

“We are delighted to collaborate with Zai Lab, including on the phase 3 innovaTV 301 trial, an important component of expanding the availability of tisotumab vedotin to recurrent or metastatic cervical cancer patients around the world. tisotumab vedotin is also under evaluation and development in early trials for first-line cervical cancer and certain other solid tumors.”

“Zai Lab has a significant presence treating women’s cancers in China, and tisotumab vedotin is an important addition to our oncology commercial portfolio. Treatments for cervical cancer remain a significant unmet need in China with approximately 110,000 new cases annually, [1] and currently there are few effective therapeutic options available,” said William Liang, Chief Commercial Officer, President of Greater China at Zai Lab.

“We look forward to this collaboration with Seagen to make tisotumab vedotin available for patients in China as we expand our oncology portfolio.”

“Following progression on first-line standard of care therapy, there are limited treatment options, and chemotherapy has low objective response rates with poor outcomes,” said Lingying Wu, MD, Ph.D, Director of the Department of Gynecologic Oncology, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.

“This represents one of the biggest challenges faced by gynecologic oncologists with significant unmet needs for new therapies. We believe tisotumab vedotin could become an important treatment option for patients with cervical cancer in China, as it demonstrated clinically meaningful, durable responses with a tolerable safety profile.”

Tisotumab vedotin is currently not approved in China, Hong Kong, Macau, and Taiwan, but, following regulatory approval is well positioned to provide a new option for previously treated advanced cervical cancer patients who currently have limited treatment options and poor outcomes.

Clinical trials
Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer (innovaTV 301) – NCT04697628

Highlights of prescribing information
Tisotumab vedotin (Tivdak®; Seagen/Genmab) [Prescribing Information]

References
[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID: 33538338.

Featured image: Detail of an artwork display at Seagen, Inc exhibition booth during the 56th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in the Moscone Center, San Francisco, CA, December 6-9, 2014.  Image Courtesy: Seattle Genetics, Inc.

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