Antibody-drug conjugate Archives - The Antibody Society

FDA approves mirvetuximab soravtansine for ovarian, fallopian tube, or primary peritoneal cancer

November 15, 2022 by Janice Reichert

The US Food and Drug Administration (FDA) granted an accelerated approval for mirvetuximab soravtansine-gynx (ELAHERE™) for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens, on November 14, 2022. FDA also approved a companion diagnostic, VENTANA FOLR1 (FOLR1-2.1) RxDx Assay, developed by Roche.

Mirvetuximab soravtansine, developed by ImmunoGen as a treatment for epithelial malignancies such as ovarian adenocarcinoma, is an antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα). The cytotoxic warhead, the tubulin-targeting maytansinoid drug DM4, is conjugated to the humanized IgG1ҡ antibody via a cleavable disulfide linker. The ADC has been granted Orphan Drug designations for ovarian cancer in the US and EU, and FDA’s Fast Track designation for a specific subset of ovarian cancer patients with medium to high FRα-positive platinum-resistant lesions who received between one and three prior systemic treatments, and for whom single-agent chemotherapy is appropriate as the next line of therapy.

FDA’s approval was based on positive results of the Phase 3 SORAYA study (NCT04296890), which evaluated the efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant advanced high-grade epithelial ovarian, primary peritoneal or fallopian tube cancer, whose tumors express a high-level of FRα. A total of 106 platinum-resistant ovarian cancer patients with high FRα expression previously treated with at least one, but less than three prior systemic treatments, at least one of which included bevacizumab, received mirvetuximab soravtansine (6 mg/kg adjusted ideal body weight) administered on day 1 of every 3-week cycle. Results from the SORAYA trial were presented at the Society of Gynecologic Oncology (SGO) annual meeting held in March 2022. Additional efficacy analyses based on a 120-day cut-off date showing tumor reduction in 71.4% of patients, an objective response rate of 32.4% as assessed by the investigator, and a preliminary median OS of 13.8 months were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting held June 3-7, 2022. A retrospective safety analysis based on 464 patients with FRα positive, recurrent ovarian cancer pooled across three studies (a Phase 1 first-in-human trial and the Phase 3 FORWARD I and SORAYA trials) demonstrating a differentiated and consistent safety profile was also presented at the 2022 ASCO meeting.

Mirvetuximab soravtansine was also evaluated in the randomized Phase 3 FORWARD I trial (NCT02631876), which enrolled 366 patients with platinum-resistant ovarian cancer, randomized 2:1 to receive either the ADC or the physician’s choice of pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel. Improved patient-reported outcomes associated with mirvetuximab compared with chemotherapy were presented at the European Society for Medical Oncology (ESMO) in held in Paris, France in September 2022. In addition, ImmunoGen continues to enroll patients in the randomized, open-label Phase 3 MIRASOL study (NCT04209855), which is evaluating mirvetuximab soravtansine vs. investigator’s choice of chemotherapy in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression. Top-line data from the confirmatory MIRASOL study are expected to be announced in early 2023. If positive, the results may support a full approval by FDA.

Interested in more information about approved antibody therapeutics? Explore our searchable table of antibody therapeutic products for details.

Tisotumab vedotin approved by FDA for cervical cancer

September 21, 2021 by Janice Reichert

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

April 26, 2021 by Janice Reichert

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

August 7, 2020 by Janice Reichert

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’.

Like this post but not a member? Please join!