Orphan drug designation has been granted by the FDA to XMT-2056 for the treatment of patients with gastric cancers.
The FDA granted an orphan drug designation to XMT-2056, an immunosynthen STING-agonist antibody-drug conjugate (ADC), for the treatment of patients with gastric cancers, according to Mersana Therapeutics.1
XMT-2056 revealed more than 100-fold increased potency compared to the free STING-agonist payload. Using mice, XMT-2056 displayed robust anti-tumor immune activity, showing only minimal increases in systemic cytokine levels, and the treatment exhibited significant benefit over the benchmark free STING-agonist payload.
Within vitro and in vivo studies, XMT-2056 was shown to be able to activate the STING pathway in both tumor-resident immune cells and tumor cells, offering a potential advantage over other innate immune activating pathways. Investigators discovered XMT-2056 was well-tolerated in non-human primates at significantly higher exposure levels than those required for anti-tumor activity, and the ADC presented favorable pharmacokinetics after repeat doses.2
Gastric cancer accounts for approximately 1.5% of all new cancers diagnosed in the United States each year, according to the American Cancer Society.
“The FDA’s decision to grant orphan drug designation to XMT-2056 for the treatment of gastric cancer is an important recognition of its potential in this area of high unmet medical need,” said Anna Protopapas, president, and chief executive officer of Mersana Therapeutics in the press release. “We are eager to bring XMT-2056 and its unique mechanism of action into the clinic mid-year to investigate its safety, tolerability and anti-tumor activity in gastric and other cancers.”
The company designed XMT-2056 to offer a differentiated and complementary therapeutic approach to existing and emerging solid tumor treatments. Mersana Therapeutics developed XMT-2056, leveraging a differentiated antibody that binds to a novel HER2 epitope, which provides the opportunity for treatment as a monotherapy and in combination with other agents, including other anti-HER2 therapies.
The company aims to initiate a phase 1 trial of XMT-2056 in a range of HER2 expressing tumors, such as breast, gastric and non–small-cell lung cancers, during 2022.
Mersana has previously developed and are in the process of testing other ADC’s such as, upifitamab rilsodotin (UpRi), a Dolaflexin ADC targeting NaPi2b that is being studied in UPLIFT (NCT03319628),3 a single-arm registrational trial in patients with platinum-resistant ovarian cancer, as well as in UPGRADE (NCT04907968),4 a phase 1/2 umbrella trial evaluating upifitamab rilsodotin in combination with other ovarian cancer therapies. Mersana has another early-stage program: XMT-1660, a Dolasynthen ADC targeting B7-H4.
PD-L1 Provides Valid Biomarker for Nivolumab/Chemo in Gastric Cancer
February 28th 2024In a discussion with Targeted Oncology, Michael Gibson, MD, PhD, discusses the benefits of using a patient’s PD-L1 combined positive score to determine if they are given nivolumab and chemotherapy to treat their gastric cancer.
Read More
Optimal Results: Neoadjuvant Durvalumab and Chemotherapy Drive Improvement in Gastric/GEJ Cancers
January 19th 2024The combination of neoadjuvant FLOT with durvalumab demonstrated enhanced pathological complete response compared to sole chemotherapy in individuals with resectable gastric and GEJ cancers, regardless of geographical location.
Read More
FDA Issues Complete Response Letter to Zolbetuximab BLA in GI Cancer
January 9th 2024The FDA has issued a complete response letter to the biologics license application of zolbetuximab for patients with advanced, HER2-negative, claudin 18.2-positive gastric or gastoesophageal junction adenocarcinoma.
Read More
FDA Approves Pembrolizumab/Chemo for Gastric and GEJ Adenocarcinoma
November 16th 2023Pembrolizumab and fluoropyrimidine- and platinum-containing chemotherapy are now FDA-approved for the treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
Read More