Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 2594 |
| INN | Upinitatug rilsodotin, Upifitamab rilsodotin |
| Status | Terminated |
| Drug code(s) | XMT-1536 |
| Brand name | None |
| 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 | Dolaflexin polymer scaffold |
| Ave. DAR | 10 to 15 drugs per mAb |
| Conjugated/fused moiety | Tubulin inhibitor, Auristatin F-hydroxypropylamide |
| Discovery method/technology | None |
| Target(s) | NaPi2b |
| Indications of clinical studies | Ovarian cancer, Cancers Likely to Express NaPi2b |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Terminated at Phase 3 |
| Status | Inactive |
| Start of clinical phase (IND filing or first Phase 1) | December 12, 2017 |
| Start of Phase 2 | |
| Start of Phase 3 | June 23, 2022 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | None |
| Date of first US approval | |
| INN, US product name | None |
| US or EU approved indications | None |
| Company | Mersana Therapeutics Inc. |
| Licensee/Partner | None |
| Comments about company or candidate | July 2023: UPLIFT trial did not meet endpoint. Mersana’s restructuring plan includes a wind-down of UpRi-related development activities, including its UP-NEXT and UPGRADE-A clinical trials and the company’s regulatory and commercial readiness efforts. If analyses of data enable the identification of a path forward for UpRi, the company will consider strategic alternatives for the asset, including partnering. June 15, 2023: Mersana Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has issued a partial clinical hold pausing new patient enrollment in UP-NEXT and UPGRADE-A, the company’s ongoing clinical trials of UpRi in platinum-sensitive ovarian cancer. Mersana’s recent assessment determined that serious bleeding events appear to occur at a higher rate than background. While most bleeding cases in this aggregate safety analysis were low-grade, five (<1%) Grade 5 (fatal) bleeding events were observed among the approximately 560 patients dosed to date. The causes of bleeding events remain under investigation. Dec 2022: European Commission (EC) has designated upifitamab rilsodotin (UpRi) as an orphan medicinal product for the treatment of ovarian cancer. NCT05329545 UP-NEXT, a Phase 3 trial of UpRi monotherapy maintenance in platinum-sensitive recurrent ovarian cancer with a design informed by FDA and CHMP feedback, due to start May 26, 2022. NCT04907968 Phase 1/2 in ovarian cancer started in April 2021. Jan 2021: “2021 promises to be another transformative year for Mersana’s pipeline. Our focus will be to initiate the UPLIFT single-arm registration strategy for XMT-1536 in platinum-resistant ovarian cancer and to initiate the UPGRADE combination umbrella study with the goal of informing the path into earlier lines of ovarian cancer therapy. Aug 2020: The FDA granted fast track designation to XMT-1536 for the treatment of women with high-grade serous ovarian cancer, according to a press release from the agent’s manufacturer. Phase 1 study still recruiting as of Aug 2019. Sep 2018: Mersana and the FDA reached alignment on changes to XMT-1522's study protocol, including increased monitoring as well as the exclusion of patients with advanced hepatic impairment. Although XMT-1536, Mersana’s Dolaflexin ADC targeting NaPi2b, was not subject to a clinical hold, Mersana has decided to implement similar modifications to the XMT-1536 protocol. Alternative dosing regimens will be evaluated for both clinical trials. NCT03319628 and NCT06517433 are both First-in-Human Studies of XMT-1536 in Cancers Likely to Express NaPi2b started in Dec 2017. XMT-1536 uses Mersana’s proprietary Dolaflexin platform to generate an ADC with a drug to antibody ratio (DAR) of 12-15. |
| Full address of company | 840 Memorial Drive, Cambridge, MA 02139 North America United States of America https://www.mersana.com/contact/ |
XMT-1536 is a highly potent immunoconjugate targeting the sodium-dependent phosphate transport protein (NaPi2b) and is comprised of an average of 10-15 DolaLockTM payload molecules conjugated to XMT-1535, a proprietary humanized anti-NaPi2b antibody, via the Dolaflexin ADC platform. NaPi2b is an antigen highly expressed in the majority of non-squamous NSCLC and epithelial ovarian cancer. https://www.gog.org/wp-content/uploads/2021/04/04-ADC-Napi2b-as-the-Target-Presentation.pdf
| Anticipated events | None |
| Factor(s) contributing to discontinuation | None |