An investigational new drug application has been cleared by the FDA for NXP800 as treatment of various advanced cancers.
Trial: A Phase 1 Clinical Study of NXP800 in Subjects With Advanced Cancers
Recruitment Status: Active, Recruiting
Description: This is a dose escalation by cohort study of NXP800 administered to patients with advanced cancers. The study will identify the maximum tolerated dose and propose dose and dose schedules for future studies.
Intervention Model: Sequential Assignment
ClinicalTrials.gov Indentifier: NCT05226507
The FDA has provided clearance to an investigational new drug (IND) application for NXP800 to be assessed as a possible treatment for patients with various advanced cancers, including a phase 1 clinical trial protocol, according to Nuvectis Pharma, Inc.1
Currently, phase 1a of the trial (NCT05226507) is ongoing in the United Kingdom.With the IND cleared by the FDA, clinical sites throughout the United States will now be included in the trial.
“The FDA approval of the IND for NXP800 marks an important milestone towards our mission of developing novel treatments for unmet medical needs in oncology,” said Ron Bentsur, chairman and chief executive officer of Nuvectis Pharma, Inc., in the press release. “We continue to effectively execute our clinical development strategy for NXP800, with the hope of it becoming the first drug approved for ARID1A-mutated ovarian clear cell carcinoma and endometrioid ovarian carcinoma, and potentially for additional cancers of unmet medical need.”
NXP800 is a novel, oral heat shock factor 1 (HSF1) pathway inhibitor that has been used for cancer cell growth, metastasis, and survival across several cancer types. Previous preclinical studies of NXP800 have shown the HSF1 pathway inhibitor to demonstrate potent anti-proliferative activity against various cancer cell lines as well as inhibit tumor growth in ARID1A-mutated ovarian clear cell carcinoma and ovarian endometrioid carcinoma human xenograft models.
The phase 1 trial evaluating the safety profile of NXP800 consists of 2 parts with phase 1a being the dose-escalation portion and phase 1b consisting of the expansion part of the study.2
Phase 1a is evaluating the safety and tolerability of NXP800 in advanced solid tumors in order to identify a dose and dosing schedule for the phase 1b portion of the study. In the phase 1b portion of the study, the safety and preliminary anti-tumor activity of NXP800 will be evaluated, first in patients with ARID1A-mutated ovarian clear cell carcinoma and ovarian endometrioid carcinoma. Additional arms are expected to be added based on the results of the ongoing in vivo studies in other tumor types.
In the ongoing dose-escalation arm of the study, a total of 7 dose levels are planned with a starting dose level of 50 mg/day and a maximum planned dose of up to 150 mg twice a day. Approximately 17 patients are expected to be enrolled in the study.
Enrollment in the trial is open to patients aged 18 years and older with histologically or cytologically confirmed, advanced, metastatic, and/or progressive solid tumors for whom no treatments are available. Further baseline characteristics include a life expectancy of 12 weeks or more, measurable disease according to RECIST 1.1., and an ECOG performance status of 0 to 2. Those with treated brain metastases are eligible to enroll in the study if there is no evidence of progression for at least 28 days after treatment.
Primary end points of the dose-escalation portion of the trial include the number of patients with treatment-related adverse events and/or clinical laboratory abnormalities and the number of patients who experience dose-limiting toxicities as defined in the protocol. Secondary end points include the area under the concentration-time curve of NXP800, maximum observed concentration of NXP800, time to peak concentration, and half-life of NXP800.
Phase 1b of the study is expected to begin in early 2023.
Additionally, Nuvectis Pharma, Inc. is currently conducting multiple in vivo studies which look to examine the potential use of NXP800 in a variety of tumor types, including gastric, liver and esophageal cancers, with and without ARID1A mutations and other biomarkers. The company hopes that NXP800 will potentially become a first-in-class inhibitor of the HSF1 pathway.
“We look forward to building on the substantial interest that NXP800 has garnered in the medical community and to working with leading clinical centers in the [United States] and the [United Kingdom] on this important project,” added Bentsur in the press release.
