Resources for For Clinicians

Ado-trastuzumab emtansine (Kadcyla®)

• Received prior therapy for metastatic disease, or
• Developed disease recurrence during or within six months of completing adjuvant therapy

Belantamab mafodotin (Blenrep™)

• Belantamab mafodotin (Blenrep™)
• Blenrep REMS (Risk Evaluation and Mitigation Strategy)
• Access & reimbursement enrollment form (United States Only)

* In November 2022, after an update from the phase 3 DREAMM-3 study the use of belantamab monotherapy for previously treated patients with relapsed or refractory multiple myeloma was pulled from US market authorization by request of the US Food and Drug Administration (FDA).

Brentuximab Vedotin (Adcetris®)

• Classical Hodgkin lymphoma (HL) after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates.
• Classical HL at high risk of relapse or progression as post auto-HSCT consolidation treatment.
• Systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen.
• The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Additional information:

• Brentuximab Vedotin
• Brentuximab Vedotin (Updates)

Enfortumab Vedotin-ejfv (Padcev™)

Additional Information

• Enfortumab vedotin-ejfv (Padcev™) / HCP
• Patient Assistant Program

Fam-trastuzumab deruxtecan-nxki (Enhertu®)

• Fam-trastuzumab deruxtecan-nxki (Enhertu®) – Patient Information
• Fam-trastuzumab deruxtecan-nxki (Enhertu®) – HCP

Gemtuzumab Ozogamicin (Mylotarg®)

Second: 2017

• Gemtuzumab Ozogamicin

Inotuzumab Ozogamicin (Besponsa®)

• Inotuzumab Ozogamicin

Loncastuximab tesirine-lpyl (Zynlonta^®)

• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, B-Cell

Loncastuximab tesirine
Loncastuximab tesirine consists of a humanized IgG1 kappa monoclonal antibody conjugated to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxic alkylating agent, through a protease-cleavable valine-alanine linker. SG3199 attached to the linker is designated as SG3249, also known as tesirine.

Loncastuximab tesirine has an approximate molecular weight of 151 kDa. An average of 2.3 molecules of SG3249 are attached to each  antibody molecule. The drug is produced by chemical conjugation of the antibody and small molecule components. The antibody is produced by mammalian (Chinese hamster ovary) cells, and the small molecule components are produced by chemical synthesis.

Loncastuximab tesirine (for injection) is supplied as a sterile, white to off-white, preservative-free, lyophilized powder, which has a cake-like appearance, for intravenous infusion after reconstitution and dilution. Each single-dose vial delivers 10 mg of loncastuximab tesirine, L-histidine (2.8 mg), L-histidine monohydrochloride (4.6 mg), polysorbate 20 (0.4 mg), and sucrose (119.8 mg).

After reconstitution with 2.2 mL Sterile Water for Injection, USP, the final concentration is 5 mg/mL with a pH of approximately 6.0.

Mechanism of Action
Upon binding to CD19, Loncastuximab tesirine  is internalized into the tumor cell and the PBD dimer cytotoxin is released into the cell. The PBD dimer binds to the DNA minor groove and forms highly cytotoxic DNA interstrand crosslinks. DNA interstrand crosslinks subsequently induce tumor cell death

Regulatory approval
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

US Food and Drug Administration
Loncastuximab tesirine-lpyl was approved for medical use in the United States in April 2021.

European approval
On 15 September 2022, 15, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product loncastuximab tesirine. Marketing authorization was granted on December 20, 2022. Marketing authorization for the agent was issued on December 20, 2022. However, loncastuximab tesirine received a Conditional marketing authorization because the approval of a medicine that addresses unmet medical needs of patients on the basis of less comprehensive data than normally required. The available data must indicate that the medicine’s benefits outweigh its risks and the applicant should be in a position to provide the comprehensive clinical data in the future. Conditional marketing authorization was granted in the interest of public health because the medicine addresses an unmet medical need and the benefit of immediate availability outweighs the risk from less comprehensive data than normally required.

In Europe, Loncastuximab tesirine is no longer an orphan medicine. It was originally designated an orphan medicine on 20 August 2021. The product was withdrawn from the Union Register of orphan medicinal products by the European Commission in November 2022 at the time of the granting of a marketing authorization.

• Loncastuximab tesirine-lpyl (Zynlonta^®)

Mirvetuximab Soravtansine-gynx (Elahere®)

Mirvetuximab soravtansine (Elahere®; previously known as IMGN853) is a first-in-class ADC comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin-targeting agent to kill the targeted cancer cells.

The US Food and Drug Administration (FDA) granted accelerated approval for the treatment of adult patients with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens.

Mirvetuximab soravtansine was approved under FDA’s accelerated approval program based on objective response rate (ORR) and duration of response (DOR) data from the pivotal SORAYA trial. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Mirvetuximab soravtansine is a first-in-class ADC directed against FRα, a cell-surface protein highly expressed in ovarian cancer, and is the first FDA approved ADC for platinum-resistant disease.

History In June 2018, the FDA granted mirvetuximab Fast Track designation for the treatment of patients with medium to high FRα-positive platinum-resistant ovarian cancer who received at least one, but no more than three prior systemic treatment regimens, and for whom single-agent chemotherapy is appropriate as the next line of therapy. This designation is intended to facilitate the development and expedite the review of drugs to treat serious and life-threatening conditions.

In December 2019, the Company (ImmunoGen) announced that FDA advised that a new single-arm study in platinum-resistant ovarian cancer could support accelerated approval for mirvetuximab. Based on this guidance, the Company initiated SORAYA, a pivotal trial to evaluate mirvetuximab monotherapy in women with FRα-high platinum-resistant ovarian cancer who have been previously treated with bevacizumab (Avastin®; Genentech/Roche). Positive top-line data for SORAYA was announced in November 2021.

Confirmation studies ImmunoGen is concurrently enrolling MIRASOL, the Phase 3 randomized confirmatory study of mirvetuximab in patients with FRα-high platinum-resistant ovarian cancer who have been treated with up to three prior regimens. Mirvetuximab monotherapy is also being studied in later line platinum-sensitive ovarian cancer and in combination in both platinum-resistant and platinum-sensitive disease.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

• Mirvetuximab soravtansine (Elahere®)

Polatuzumab Vedotin-piiq (Polivy™)

Sacituzumab Govitecan-hziy (Trodelvy™

• Sacituzumab Govitecan-hziy (Trodelvy™)

Tisotumab vedotin-tftv (Tivdak® )

• Tisotumab vedotin-tftv (Tivdak® )