Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 80 |
| INN | Sacituzumab govitecan |
| Status | Approved |
| Drug code(s) | IMMU-132, hRS7-SN-38 |
| Brand name | Trodelvy |
| mAb sequence source | mAb humanized |
| General Molecular Category | ADC |
| Format, general category | Full length Ab conjugate |
| Format details | None |
| Isotype (Fc) | IgG1 |
| Light chain isotype | kappa |
| Linker | CL2A, Cleavable linker |
| Ave. DAR | 7 to 8 drugs per mAb |
| Conjugated/fused moiety | Topoisomerase I inhibitor, SN38 (irinotecan active metabolite) |
| Discovery method/technology | None |
| Target(s) | TROP-2 |
| Indications of clinical studies | Triple negative breast cancer, metastatic urothelial cancer, Advanced Epithelial Cancers |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Approved EU, US, Australia |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | June 01, 2012 |
| Start of Phase 2 | |
| Start of Phase 3 | October 12, 2017 |
| Date BLA/NDA submitted to FDA | May 18, 2018 |
| Year of first approval (global) | 2020 |
| Date of first US approval | April 22, 2020 |
| INN, US product name | Sacituzumab govitecan, sacituzumab govitecan-hziy |
| US or EU approved indications | US: First approval for Triple-Negative Breast Cancer (TRODELVY is indicated for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease). US Supplemental approvals (as of November 22, 2024 label)) for Locally Advanced or Metastatic Breast Cancer (TRODELVY is indicated for the treatment of adult patients with Locally Advanced or Metastatic Breast Cancer: Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease or, Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrinebased therapy and at least two additional systemic therapies in the metastatic setting.) US: Marketing approvals withdrawn for Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PDL1) inhibitor. EU: First approval for Triple-Negative Breast Cancer. Supplemental approval for Breat Cancer (TRODELVY as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, including at least one of them for advanced disease. TRODELVY as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have received endocrine-based therapy, and at least two additional systemic therapies in the advanced setting.). (as per EPAR - Product information last updated on August 11, 2023). |
| Company | Immunomedics Inc. |
| Licensee/Partner | Seagen Inc. |
| Comments about company or candidate | Oct 18, 2024: Gilead Sciences is voluntarily withdrawing its drug, Trodelvy, for patients with metastatic urothelial cancer after it failed to meet the main goal in a confirmatory trial. The U.S. Food and Drug Administration had granted accelerated approval to Trodelvy for previously treated patients with metastatic urothelial cancer in 2021, while its continued approval was dependent on results of a confirmatory trial. Approved in EU in Nov 2021. FY 2020 FDA report to congress: 1st cycle 8.0 months; Sponsor 10.5 months; 2nd cycle 4.7 = total time 23.2 PDUFA date June 2, 2020. April 2020: Immunomedics announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for sacituzumab govitecan for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting, including patients who are platinum ineligible and have previously received a PD-1 or PD-L1 inhibitor in the neoadjuvant/adjuvant, locally advanced, or metastatic setting. Aug 2019: Resubmission of Biologics License Application on Track for Early Fourth Quarter 2019. January 2019: Complete response letter details CMC issues to be addressed. July 2018: U.S. Food and Drug Administration (FDA) has accepted the Company’s Biologics License Application (BLA) for filing and granted Priority Review for sacituzumab govitecan for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who previously received at least two prior therapies for metastatic disease. The PDUFA target action date is January 18, 2019. January 8, 2018 --- Immunomedics, Inc., and Royalty Pharma today announced that Immunomedics has agreed to sell tiered, sales-based royalty rights on global net sales of sacituzumab govitecan to Royalty Pharma for $175 million. SG deal placed on hold in March 2017 after a shareholder revolt. Disgruntled investors—led by activist investor venBio—eventually forced through changes to the biotech's board of directors. Feb 2017: Seattle Genetics will be responsible for initiating the Phase 3 clinical trial of IMMU-132 in patients with metastatic triple-negative breast cancer (TNBC) and submitting the initial Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for accelerated approval. The agreement includes the development of additional indications for IMMU-132, including urothelial cancer (UC), small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), which are currently in Phase 2 clinical studies, along with other solid tumor indications being studied in ongoing clinical trials. NCT02574455 Phase 3 study recruiting as of Oct 2017. April 2016: objective durable responses have been achieved with sacituzumab govitecan in a number of patients with advanced, metastatic solid cancers, after failing multiple prior therapies, some including checkpoint inhibitors (CPIs). The antibody-drug conjugate sacituzumab govitecan from Immunomedics has received breakthrough therapy designation by the FDA as a treatment candidate for patients with triple-negative breast cancer who have not responded to other therapies for metastatic disease. Fast track designations for triple-negative breast cancer, non-small cell and small cell lung cancer. Phase 2 study in breast cancer due to start in Aug 2014. Phase 1/2 study NCT01631552 started in Feb 2013; Immunomedics presentation of mid-2012 notes that 'For hRS7-SN-38, we have FDA approval to study in a variety of cancer types…'. US orphan drug designation for small cell lung cancer. As per earnings call on Feb 11, 2014, Immunomedics is discussing outlicensing with potential partners. IMMU-132 has received orphan drug status from the Office of Orphan Products Development of the U.S. Food and Drug Administration (FDA) for the treatment of pancreatic cancer. Orphan designation in EU for pancreatic cancer. June 1, 2012: Original IND submission to evaluate of sacituzumab (IMMU-132, hRS7-SN38) in patients with advanced epithelial malignancies (IND 115621). |
| Full address of company | 333 Lakeside Drive Foster City, CA 94404 North America United States of America https://www.gilead.com/utility/contact |
Sacituzumab govitecan-hziy is a Trop-2 directed antibody and topoisomerase inhibitor conjugate, composed of the following three components: a) the humanized monoclonal antibody, hRS7 IgG1κ (also called sacituzumab), which binds to Trop-2 (the trophoblast cell-surface antigen-2); b) the drug SN-38 (irinotecan active metabolite), a topoisomerase inhibitor; c) a hydrolysable linker (called CL2A), which links the humanized monoclonal antibody to SN-38.
The recombinant monoclonal antibody is produced by mammalian (murine myeloma) cells, while the small molecule components SN-38 and CL2A are produced by chemical synthesis. Sacituzumab govitecan-hziy contains on average 7 to 8 molecules of SN-38 per antibody molecule. Sacituzumab govitecan-hziy has a molecular weight of approximately 160 kilodaltons.
| Anticipated events | None |
| Factor(s) contributing to discontinuation | None |