NXP800 Demonstrates Single-Agent Activity in ARID1a+ Platinum-Resistant Ovarian Cancer

Ron Bentsur, chairman and CEO of Nuvectis Pharma

The oral, small molecule, potentially first-in-class GCN2 kinase activator NXP800 generated antitumor activity as monotherapy in patients with platinum-resistant ovarian cancer harboring ARID1a mutations, according to interim data from a phase 1b trial (NCT05226507).¹

Findings announced by Nuvectis Pharma showed that among efficacy-evaluable patients (n = 11), NXP800 produced an unconfirmed partial response in 1 patient. Six patients experienced stable disease with tumor shrinkage.

“We continue to be encouraged by the early results from our phase 1b study with NXP800. The antitumor activity observed despite patients’ advanced disease and extensive pretreatment, while controlling for thrombocytopenia, is promising,” Ron Bentsur, chairman and CEO of Nuvectis Pharma, stated in a news release. “However, it is clear that we need to increase the dose intensity to drive more efficacy in the next set of patients. We are already enrolling patients into a cohort of up to 10 to 12 additional patients utilizing a regimen of 75 mg [per] day on an intermittent dosing schedule, which is expected to be the last cohort in this phase 1b study.”

Previously reported data from the phase 1b study showed that among 4 patients treated with continuous NXP800, 3 experienced grade 4 thrombocytopenia. Consequently, an intermittent dosing schedule of 50 mg per day for 5 days on and 2 days off was utilized for the next 8 patients; in this group, the highest grade of thrombocytopenia observed was a grade 2 event in 1 patient. Most treatment-emergent adverse effects were grade 1 and 2, and the most common included nausea, fatigue, vomiting, diarrhea, and constipation.

Previously, the FDA granted orphan drug designation to NXP800 for the treatment of patients with ARID1a-deficient ovarian, fallopian tube, and primary peritoneal cancers.

Part A of the phase 1 study included patients at least 18 years of age with histologically or cytologically confirmed advanced, metastatic, and/or progressive solid tumors with no available standard therapies, or for whom standard therapies are inappropriate.² Patients needed to have measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 to 2, and a life expectancy of at least 12 weeks.

Part B included patients with ARID1a-mutated ovarian, fallopian tube, or primary peritoneal cancer who experienced disease progression within 6 months of completing platinum-based chemotherapy. One to 3 prior lines of systemic lines of anticancer therapy, including at least 1 containing bevacizumab (Avastin), were required, and those harboring BRCA mutations needed to have prior treatment with a PARP inhibitor. Key inclusion criteria for this part consisted of measurable disease per RECIST 1.1 criteria and an ECOG performance status of 0 or 1.

The 12 patients treated thus far in part B have received NXP800 on 1 of 3 dosing schedules: 75 mg per day (n = 2), 50 mg per day (n = 2), and 50 mg per day for 5 days on and 2 days off (n = 8).¹

Safety and overall response rate per RECIST 1.1 criteria were the primary end points for part B.²

All patients enrolled into part B experienced disease progression after at least 2 prior lines of systemic chemotherapy, including at least 1 platinum-based chemotherapy regimen.1 Most patients had also progressed after prior bevacizumab.

“We believe that NXP800 is an active agent and that this higher dose intensity should provide for increased exposure that could enable us to reach our goal of demonstrating enhanced activity with acceptable overall tolerability,” Bentsur added in the news release. “We expect to provide additional clinical data from the phase 1b study in the second quarter of 2025.”

References

1. Nuvectis Pharma reports encouraging NXP800 interim data supporting ongoing enrollment in phase 1b study in patients with platinum-resistant ARID1a-mutated ovarian cancer. News release. Nuvectis Pharma. November 14, 2024. Accessed November 14, 2024. https://nuvectis.com/press-release-view/?i=140268
2. A phase 1 clinical study of NXP800 in subjects with advanced cancers and expansion in subjects with ovarian cancer. ClinicalTrials.gov. Updated September 19, 2024. Accessed November 14, 2024. https://clinicaltrials.gov/study/NCT05226507