Osemitamab Gains FDA Orphan Drug Status for Pancreatic Cancer


Based on findings from a phase 1 trial, osemitamab has gained an orphan drug designation from the FDA for the treatment of patients with pancreatic cancer.

The FDA has granted an orphan drug designation (ODD) to osemitamab (TST001) for patients with pancreatic cancer, according to Transcenta Holding Limited.1

This marks the second ODD granted to osemitamab. The first was given in July 2021 for the treatment of patients with gastric cancer and gastroesophageal junction cancer.1

This designation is based on findings previously reported at the 2022 International Gastric Cancer Congress which showed osemitamab monotherapy prolonged partial responses (PRs) in patients with Claudin18.2 low-expressing pancreatic cancer who progressed after multiple cycles of chemotherapy.2

"Osemitamab is currently being evaluated for the treatment of different Claudin18.2 positive indications. We believe it also has the potential to be transformative for [patients with] advanced pancreatic adenocarcinoma who lack effective therapeutic options. We look forward to progressing our program in this indication." said Caroline Germa, MD, executive vice president and global medicine development and chief medical officer of Transcenta Holding Limited, in a press release.

Osemitamab is a high affinity humanized anti-Claudin18.2monoclonal antibody that has enhanced antibody-dependent (ADCC) cellular cytotoxicity (CDC) and complement-dependent cytotoxicity activities. In tumor xenograft models, the antibody has had potent anti-tumor activities as well. Osemitamab was developed to eliminate Claudin18.2 expressing tumor cells by mechanisms of ADCC and CDC.

Preclinical studies of osemitamab have shown potent anti-tumor activities in Claudin18.2 expressing pancreatic cancer tumor models independent of KRAS mutation status. Additionally, an ongoing trial is assessing treatment with osemitamab for patients with advanced or metastatic solid tumors (NCT04396821) in the United States and China.

In another open-label, phase 1 study (NCT04495296), patients with locally advanced or metastatic solid tumors are being evaluated to determine the safety, tolerability, pharmacokinetics (PK), and efficacy of osemitamab.2

The dose-escalation phase of the trial gave patients without pre-selection of tumor Claudin18.2 expression increasing doses of osemitamab via intravenous infusion every 3 weeks using a 3+3 design. A total of 11 patients were treated at dose levels consisting of 3 mg, 6 mg, and 10 mg every 3 weeks as of November 23, 2021. Nine patients were evaluable for dose-limiting toxicity. At this point, no DLTs were reported and the maximum tolerated dose (MTD) had not been reached.

Investigators sought to evaluate the primary end points of safety and tolerability of osemitamab, and to identify the MTD and recommended phase 2 dose (RP2D) of the agent in patients with advanced or metastatic solid tumors who progressed on or after standard treatments. Secondary end points of the trial assessed PK, immunogenicity, and preliminary anti-tumor activity.

According to findings from the 2022 International Gastric Cancer Congress, osemitamab had a roughly linear PK profile. Both the Cmax and area under the curve increased proportionally across the dose range after treatment with the first dose. Treatment with osemitamab 10 mg/kg every 3 weeks was designated as the RP2D and was further evaluated in the expansion portion of the trial in which additional patients with Claudin18.2 overexpression were enrolled.

In the 6-mg/kg every-3-weeks dose-escalation cohort of patients who progressed on multiple lines of chemotherapies, anti–PD-1, and anti-VEGF therapies, 1 patient achieved a confirmed PR at week 12. After the data cut-off date, other patients in the newly enrolled monotherapy expansion cohorts had confirmed PRs when treated at the RP2D. These cohorts consisted of patients with gastric cancer and pancreatic cancer who had Claudin18.2 expression. Further, 1 patient with pancreatic cancer with medium-low Claudin18.2 expression reached 82% tumor reduction at 12 weeks post-treatment.

Looking at safety, the most common adverse events (>20%) were nausea, vomiting, anemia, hypoalbuminemia, abdominal distension, and constipation.

Overall, this phase 1 clinical study of osemitamab showed a manageable and tolerable safety profile in patients with advanced solid tumors, as well as preliminary antitumor activity in a heavily pretreated patient with gastric and pancreatic cancer expressing Claudin18.2.

Transcenta's osemitamab (TST001) targeting Claudin18.2 granted orphan drug designation for treatment of pancreatic cancer. News release. Transcenta Holding Limited. March 29, 2023. Accessed March 30, 2023. https://prn.to/3Zz7k7n
Transcenta presented safety / tolerability and preliminary anti-tumor activity data in gastric and pancreatic cancers of TST001 monotherapy from China phase I clinical trial at the 2022 international gastric cancer congress. News release. Transcenta Holding Limited. March 09, 2022. Accessed March 30, 2023. https://prn.to/3KnxeXK
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