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Tisotumab vedotin approved by FDA for cervical cancer

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On September 20, 2021, FDA granted accelerated approval to TIVDAK (tisotumab vedotin-tftv) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The BLA for TIVDAK for this indication was given a Priority review. TIVDAK’s approval was based on tumor response and the durability of the response; verification and description of clinical benefit in confirmatory trials may be necessary for continued approval for this indication.

TIVDAK is an ADC comprising Genmab’s human tissue factor IgG1k antibody targeting tissue factor conjugated to MMAE via a protease-cleavable linker using Seagen’s ADC technology. The companies are co-developing the product. The recommended dose of TIVDAK is 2 mg/kg (up to a maximum of 200 mg) given as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.

FDA’s approval was based on results of the pivotal single-arm Phase 2 innovaTV 204 study (NCT03438396), which included 101 patients 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 chemotherapy regimen. Patients received tisotumab vedotin 2.0 mg/kg IV every 3 weeks  until progression or toxicity. The major efficacy outcome measures were confirmed objective response rate as assessed by an independent review committee using RECIST v1.1 criteria and duration of response (DOR). The objective response rate was 24% [95% CI: 15.9%-33.3%], including 7 patients (7%) with a complete response and 17 patients (17%) with a partial response, and the median DOR was 8.3 months (95% CI: 4.2, not reached).

TIVDAK is the 9th antibody therapeutic to be first approved for marketing in the EU or US in 2021. Explore our searchable table of antibody therapeutics approved in the US or EU for details.

Loncastuximab tesirine granted first approval by FDA for large B-cell lymphoma

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On April 23, 2021, the  US Food and Drug Administration (FDA) granted accelerated approval to loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics SA) for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma. This marketing application was granted priority review and orphan drug designation by FDA. The review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Loncastuximab tesirine (ADCT-042) is an antibody-drug conjugate composed of an anti-CD19 humanized IgG1k antibody conjugated via a linker to pyrrolobenzodiazepine-dimer toxin that induces the killing of CD19-expressing malignant B cells.

The BLA submission was supported by data from the open-label, single-arm Phase 2 LOTIS 2 study (NCT03589469), which evaluated the safety and efficacy of loncastuximab tesirine for the treatment of patients with relapsed or refractory DLBCL following ≥2 lines of prior systemic therapy. A total of 145 patients received loncastuximab tesirine as an intravenous infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg for 2 cycles, then 75 μg/kg for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria. The primary outcome measure is the overall response rate (ORR). Positive initial data from LOTIS 2 were presented during the virtual 25th Annual Congress of the European Hematology Association. The ORR was 48.3% (70/145 patients), the complete response rate was 24.1% (35/145 patients), and the median duration of response was 10.25 months. The toxicity profile was manageable and no new safety concerns were identified.

Need help keeping up to date on US and EU approvals?

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

FDA grants first approval to belantamab mafodotin-blmf

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On August 5, 2020, the U.S. Food and Drug Administration (FDA) approved belantamab mafodotin-blmf (BLENREP) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. BLENREP was granted an accelerated approval for this indication based on response rate. Further adequate and well-controlled studies/clinical trials must be done to verify and describe clinical benefit.

Belantamab mafodotin-blmf is an antibody-drug conjugate (ADC) composed of a humanized IgG1 monoclonal antibody and the cytotoxic agent maleimidocaproyl monomethyl auristatin F. The ADC binds to B-cell maturation antigen found on myeloma cell surfaces and is internalized. In the cell, the cytotoxic agent is released and kills the cells.

Belantamab mafodotin-blmf was evaluated in the Phase 2 DREAMM-2 (NCT03525678), an open-label, multicenter trial. Efficacy was based on overall response rate (ORR) and response duration. In patients receiving the recommended dose of 2.5 mg/kg, the ORR was 31% (97.5% CI: 21%, 43%) 73% of responders had response durations ≥6 months. Detailed results of the study were published in The Lancet Oncology in February 2020.

On July 24, 2020, the European Medicines Agency’s (EMA) human medicines committee recommended granting a conditional marketing authorization in the European Union for Blenrep (belantamab mafodotin) to treat adult patients with relapsed and refractory multiple myeloma who no longer respond to treatment with an immunomodulatory agent, a proteasome inhibitor and a CD-38 monoclonal antibody. Blenrep was accepted in EMA’s PRIME scheme, and it was designated as an orphan medicinal product. EMA recommended a conditional marketing authorization, and this opinion was sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization.

Antibodies to watch

Belantamab mafodotin-blmf is the 7th antibody therapeutic to be granted a first approval in the US or EU in 2020. The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format. Information about antibody therapeutics approved outside the US or EU can be found in the table notes.

Information about other antibody therapeutics that may enter regulatory review in 2020 can be found in ‘Antibodies to watch in 2020’.

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