FDA Grants Fast Track Designation to IN10018 for Platinum-Resistant Ovarian Cancer

IN10018 has received fast track designation from the FDA for the treatment of patients with platinum-resistant ovarian cancer, according to a press release from drug developer InxMed.¹

This designation is typically granted to potential new therapy options for patient populations with an unmet medical need, with investigators noting the significant treatment potential of IN10018 in platinum-resistant ovarian cancer.

“This is an important milestone for InxMed. IN10018 is one of our critical assets to fulfill our ‘Best-in-Disease Combination’ development strategy. We will leverage the advantage of Fast Track status and work closely with US FDA to speed up further clinical development,” Zaiqi Wang, chairman and CEO of InxMed, said in a press release. “InxMed will fully accelerate global clinical development of IN10018 to better meet the patient's needs.”

Currently, chemotherapy is one of the primary treatment modalities for patients with ovarian cancer with notable impact on those who receive it. However, the development of resistance followed by fast-moving progression is inevitable. Patients with platinum-resistant ovarian cancer have limited treatment options and a poor prognosis. Novel treatment options such as IN10018 may help to provide a solution when combined with standard-of-care chemotherapy.

IN10018 is both a potent and selective adenosine triphosphate–competitive focal adhesion kinase (FAK) small molecule inhibitor that is currently in clinical develop across a number of countries, including the United States, Australia, and China. The agent has yielded promising clinical findings in early data and demonstrated promising efficacy signals in several tumor types.

IN10018 was previously examined in a phase 1 study (NCT01335269) that enrolled patients (n = 41) with a number of different tumor types, including platinum-resistant ovarian cancer, advanced pancreatic adenocarcinoma, esophageal cancer, and soft tissue sarcoma. Patients received 200 mg of the agent.²

Preliminary efficacy data indicated that 8 patients achieved stable disease for 2 to 6 cycles after undergoing treatment with IN10018, including 3 with pancreatic adenocarcinoma, 1 with ovarian cancer, 1 with esophageal cancer, and 3 with soft tissue sarcoma.

Additionally, the agent demonstrated a favorable safety profile, with common treatment-related adverse effects (TRAEs) including proteinuria (58.5%), nausea (58.5%), diarrhea (48.8%), and vomiting (36.6%). A total of 8 patients experienced grade 3 proteinuria and 10 needed a dose reduction. Although 3 serious TRAEs were reported, investigators stated that none were fatal.

Investigators theorize that FAK inhibitors such as IN10018 may have the potential to overcome the fibrotic barrier and immune tolerance, which may work to boost other therapies, such as targeted therapies, chemotherapy, immunotherapy, and radiation therapy.

IN10018 is also being examined both as a monotherapy and in combination with cobimetinib (Cotellic) as part of a phase 1b study (NCT04109456) for patients with metastatic uveal melanoma and NRAS-mutant metastatic melanoma. The open-label clinical trial aims to evaluate the safety, tolerability, and antitumor activity of IN10018 both alone and as part of a combination regimen.

The trial has an estimated enrollment of 54 patients who will receive a 100-mg dose of IN10018 once daily in part 1 of the study. In part 2, in addition to being treated with IN10018, patients will be given a 60-mg dose of cobimetinib once daily from day 1 to day 21 as part of a 28-day cycle.

References

1. InxMed's IN10018 receives U.S. FDA fast track designation for the treatment of platinum-resistant ovarian cancer. News release. InxMed. August 16, 2021. Accessed August 16, 2021. https://bit.ly/3sjP8zX
2. Zer A, Verheijen R, De Vos FYL, et al. A phase I study of BI 853520, an inhibitor of focal adhesion kinase K), in patients with advanced or metastatic solid tumors. J Clin Oncol. 2015;33(suppl (FA 15):2541-2541. doi:10.1200/jco.2015.33.15_suppl.2541