Using the recommended doses of 50 and 70 mg per day from a phase 1a trial of NXP800, the agent will be further evaluated in patients with platinum-resistant, ARID1a-mutated ovarian cancer.
Trial Name: A Phase 1 Clinical Study of NXP800 in Subjects With Advanced Cancers
ClinicalTrials.gov Identifier: NCT05226507
Sponsor: Nuvectis Pharma, Inc.
Recruitment Contact: Diane Marsolini, (603) 571-0185, dmarsolini@nuvectis.com, and Shay Shemesh, MSc, (201) 614-3153, sshemesh@nuvectis.com
Completion Date: April 2023
A phase 1b study (NCT05226507) examining the safety, tolerability, and preliminary efficacy of NXP800 in patients with platinum-resistant, ARID1a-mutated ovarian carcinoma has begun.1
The phase 1b portion of the study follows positive findings from the phase 1a part which evaluated the agent in patients with advanced solid tumors.
The doses being evaluated in the phase 1b study, 50 and 75 mg per day, were chosen based on this initial portion of the trial.
In preliminary population pharmacokinetics and pharmacodynamic analyses, once daily oral administration of NXP800 at 50 and 75 mg per day achieved biologically active exposure levels and demonstrated an acceptable safety and tolerability profile.
“We are excited to announce the initiation of the phase 1b study in which NXP800 will be tested, for the first time, in patients with a target disease,” said Ron Bentsur, chairman and chief executive officer of Nuvectis, in the press release. “The robust preclinical anti-tumor activity of NXP800, coupled with the data from the phase 1a dose escalation study, led to the design of the phase 1b study, including the definition of the patient population and selection of doses and dosing schedules.”
NXP800 is an oral, small molecule inhibitor of the HSF1 pathway that has previously shown robust anti-tumor activity in xenograft models of ARID1a-mutated ovarian carcinoma, as well as in other disease models.
The NXP800 development program in platinum-resistant, ARID1a-mutated ovarian cancer was granted a fast track designation by the FDA.
The multicenter, single-agent, open-label, phase 1b trial will be conducted in 25-30 states in the United States, United Kingdom, and Europe, and plans to enroll 2 cohorts of up to approximately 25 patients each. Patients will be given 1 of 2 dose regimens, either 50 mg or 75 mg, which will be administered once daily. Dosing regimens will be elected based on data from the phase 1a dose-escalation study which is assessing the agent in patients with various types of advanced solid tumors.
Patients enrolled in the trial must be aged 18 years and older with histologically or cytologically confirmed, advanced, metastatic, and/or progressive solid tumors for whom there is no authorized or effective treatment available, or for whom such therapies are considered inappropriate by the investigator or declined by the subject, a life expectancy of 12 weeks, measurable disease, and an ECOG performance status of 2 or greater.2
Primary end points of the trial will assess the number of patients with treatment-related adverse events (TRAEs) and dose-limiting toxicities. Secondary end points of the trial are evaluating pharmacokinetics and pharmacodynamics.
In the first-in-human phase 1a study of NXP800, patients with various types of non-target, advanced solid tumors were evaluated. Eighteen patients, as of April 2023, received at least 1 dose of NXP800. The longest duration of treatment is 10 months; however, treatment is ongoing.1
Two different dosing schedules were evaluated, including a once per day schedule which utilized total daily doses of 50 mg-150 mg, and a twice per day schedule using total daily doses of 100 mg and 150 mg.
Findings from part 1a showed that the clinical profile of NXP800 was consistent with what investigators expected from the preclinical studies. The most common treatment-emergent adverse events included vomiting, nausea, diarrhea, fatigue, decreased appetite and weight decrease. Common lab abnormalities included transient changes in platelets, liver enzymes and red blood cells, which had no clinical consequences. There were no drug-related grade 4 or 5 events reported.
The company plans to share detailed results from the phase 1a study at a future scientific conference.
“Based on the totality of the data generated to date, we believe that NXP800 has the potential to become an effective treatment for patients with platinum-resistant, ARID1a-mutated ovarian carcinoma, as well as additional target tumor types, which we plan to also investigate in the near term," Bentsur concluded.
