FDA Grants Orphan Drug Designation to NXP800 for Cholangiocarcinoma

The FDA has granted an orphan drug designation to NXP800 for the treatment of patients with cholangiocarcinoma, according to an announcement from Nuvectis Pharma.1

“We are pleased to have received this designation from the FDA for NXP800, which emphasizes the need for new, innovative therapies for the treatment of cholangiocarcinoma, a deadly malignancy with only limited treatment options available. NXP800 is an oral small molecule with a novel mechanism of action that has demonstrated robust activity in several preclinical cancer models, including ARID1a-mutated ovarian, endometrial, and gastric carcinomas, as well as cholangiocarcinoma,” Ron Bentsur, chairman and chief executive officer of Nuvectis, said in a news release.

NXP800 is an oral, HSF1 pathway small molecular inhibitor that has demonstrated significant antitumor activity in xenograft models of ARID1a-mutated ovarian cancer and other solid tumor models.

In September 2022, Nuvectis released positive preclinical data for NXP800. The study, which was performed in a xenograft mouse model of ARID1a-mutated gastric cancer, demonstrated tumor volume regression and significant tumor growth inhibition with 35 mg/kg of NXP800 vs the control over the course of 28 days.3

In December 2022, the FDA granted fast track designation to NXP800 for the treatment of patients with platinum-resistant, ARID1a-mutated ovarian cancer.4

The agent is currently under investigation in a first-in-human phase 1 trial (NCT05226507).5 Previously reported results from the phase 1a portion of the trial in patients with non-target, advanced solid tumors demonstrated that 18 patients had received at least 1 dose of NXP800 as of April 2023, at which time the longest treatment duration reached 10 months.2 Two dosing schedules were evaluated: 50 mg and 150 mg once daily, and 50 mg and 75 mg twice daily, with clinical activity supporting earlier preclinical data.

Regarding safety, the most frequent adverse effects were vomiting, nausea, diarrhea, fatigue, decreased appetite, weight decrease, and lab abnormalities including changes in platelets, liver enzymes, and red blood cells, none of which were grade 4 or 5. Based on pharmacokinetic and pharmacodynamic analysis, the 50 mg and 75 mg once daily doses were selected to move forward into phase 1b.2

In April 2023, the company announced the launch of the multicenter, phase 1b portion of the study in 2 cohorts of up to 25 patients with platinum-resistant, ARID1a-mutated clear cell and endometrioid ovarian cancer.

To be eligible for enrollment in part A, patients must have been at least 18 years of age with a histologically confirmed, advanced, metastatic, and/or progressive solid tumor for which there is no authorized or effective therapy available. Life expectancy of at least 12 weeks, ECOG performance status of 2 or below, and measurable disease per RECIST v1.1 criteria were also required.

In part B, patients must be at least 18 years of age with clear cell or endometrioid ovarian carcinoma with disease progression within 6 months from completion of platinum-based chemotherapy; measurable disease per RECIST v1.1 criteria; at least 1 but no more than 3 prior lines of therapy, including bevacizumab (Avastin) and a PARP inhibitor if BRCA mutant; an ECOG performance status of 0 or 1; and sufficient archival formalin-fixed paraffin-embedded tissue specimen.5

“The clinical activity of NXP800 is currently being evaluated in a phase 1b clinical trial in patients with platinum resistant, ARID1a-mutated ovarian carcinoma, with additional diseases planned for clinical investigations,” Bentsur added. “This orphan drug designation is an important milestone in our journey toward our mission of developing NXP800 for the treatment of serious conditions of unmet medical need in oncology.”1


  1. Nuvectis Pharma announces orphan drug designation granted by the FDA to NXP800 for the treatment of cholangiocarcinoma. News release. Nuvectis Pharma. August 17, 2023. Accessed August 17, 2023. https://nuvectis.com/press-release-view/?i=121906
  2. Nuvectis Pharma announces initiation of the phase 1b study for NXP800 in platinum-resistant, ARID1a-mutated ovarian carcinoma phase 1b study builds on highly consistent preclinical and phase 1a data. Nuvectis Pharma. April 10, 2023. Accessed August 17, 2023. https://www.biospace.com/article/releases/nuvectis-pharma-announces-initiation-of-the-phase-1b-study-for-nxp800-in-platinum-resistant-arid1a-mutated-ovarian-carcinomaphase-1b-study-builds-on-highly-consistent-preclinical-and-phase-1a-data/
  3. Nuvectis Pharma announces positive data for NXP800 in a preclinical model of ARID1a-mutated gastric carcinoma. News release. Nuvectis Pharma. September 13, 2022. Accessed August 17, 2023. https://www.globenewswire.com/news-release/2022/09/13/2514986/0/en/Nuvectis-Pharma-Announces-Positive-Data-for-NXP800-in-a-Preclinical-Model-of-ARID1a-Mutated-Gastric-Carcinoma.html
  4. FDA grants fast track designation to Nuvectis Pharma’s NXP800 for the treatment of platinum-resistant, ARID1A-mutated ovarian carcinoma. News release. Nuvectis Pharma. December 1, 2022. Accessed August 17, 2023. https://www.globenewswire.com/news-release/2022/12/01/2565889/0/en/FDA-Grants-Fast-Track-Designation-to-Nuvectis-Pharma-s-NXP800-for-the-Treatment-of-Platinum-Resistant-ARID1A-Mutated-Ovarian-Carcinoma.html
  5. A phase 1 clinical study of NXP800 in subjects with advanced cancers and expansion in subjects with ovarian cancer. ClinicalTrials.gov. Updated May 18, 2023. Accessed August 17, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05226507



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