FDA Grants Fast Track Designation to Novel HSF1 Pathway Inhibitor NXP800 for Ovarian Cancer

The FDA issued a Fast Track designation to NXP800 for the treatment of patients with platinum-resistant, ARID1A-mutated ovarian cancer, according to a press release from Nuvectis Pharma.¹

NXP800 is a first-in-class, orally active Heat Shock Factor 1 (HSF1) pathway inhibitor currently under examination in a phase 1 dose-escalation study (NCT05226507).Tolerated doses of this novel agent resulted in prolonged inhibition of tumor growth as well as regression in xenografts of human clear cell and endometrial ovarian cancer. Additionally, ARID1A mutation was associated with greater therapeutic effect.²

“We are very pleased with the FDA’s decision to grant Fast Track designation to NXP800 for the treatment of platinum-resistant, ARID1A-mutated ovarian carcinoma, which underscores the potential of NXP800 to address this serious condition of unmet medical need,” said Ron Bentsur, Chairman and CEO of Nuvectis Pharma.¹

Seven dosage levels will be tested in the dose-escalation study of NXP800, starting with 50mg once per day and increasing to a planned maximum of 150mg twice per day. Investigators will assess the frequency of treatment-related adverse effects and the quantity of patients with dose-limiting toxicities at day 28 as primary end points. Secondary end points will include the maximum observed concentration, the area under the concentration-time curve, the time to peak concentration, and the half-life of the agent.

The study includes patients with advanced, metastatic, or progressive solid tumors for whom there is no authorized or appropriate treatment available. Patients must also have measurable disease according to RECIST Version 1.1 criteria, an ECOG performance status of 2 or less, and a life expectancy of at least 12 weeks to be included.

Moreover, patients must not have received endocrine therapy, chemotherapy, an investigational agent, or radiotherapy, except for palliative reasons, within 28 days of their first dose. They must also not have any ongoing toxic manifestations from prior treatments of grade 3 severity or higher to be included in the study.

Patients with brain metastases are also excluded unless they exhibit no evidence of progression for at least 28 days following a central nervous system–directed treatment.

Another novel agent, the SRC/YES1 kinase inhibitor NXP900, remains in clinical development.¹

References

1. FDA Grants Fast Track Designation to Nuvectis Pharma's NXP800 for the Treatment of Platinum-Resistant, ARID1A-Mutated Ovarian Carcinoma. News Release. Nuvectis Pharma, Inc. December 1, 2022. Accessed December 2, 2022. https://bit.ly/3VJx2on
2. Workman, P. Abstract ND08: NXP800: A first-in-class orally active, small-molecule HSF1 pathway inhibitor. Cancer Res. 2022;82(12_suppl):ND08. doi:10.1158/1538-7445.AM2022-ND08