A Phase 1 Clinical Study of NXP800 in Subjects with Advanced Cancers and Expansion in Subjects with Ovarian Cancer

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor; ARID1A Gene Mutation; Ovarian Clear Cell Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Cancer; Ovarian Clear Cell Carcinoma; Ovarian Endometrioid Tumor
• Interventions: Drug: NXP800

• Registration Number: NCT05226507
• Lead Sponsor: Nuvectis Pharma, Inc.

Brief Summary

The purpose of the dose escalation phase is to evaluate the safety profile of escalating doses and dose schedules of NXP800. In the expansion phase the preliminary efficacy in subjects with ARID1a mutated ovarian clear cell and ovarian endometrioid cancers will be estimated.

Detailed Description

Part A of the study is a dose escalation by cohort study of NXP800 administered to patients with advanced cancers. The study will identify the maximum tolerated dose (MTD) and propose dose and dose schedules for future studies.

In Part B doses selected in Part A are administered to patients with platinum-resistant, ARID1a-mutated ovarian carcinoma.

Study Timeline

• Study Start: 2021-12-31
• Study First Submitted: 2022-01-13
• Study First Submitted QC: 2022-02-04
• Study First Posted: 2022-02-07
• Status Verified: 2024-09
• Last Update Submitted: 2024-11-22
• Last Update Posted: 2024-11-26
• Primary Completion: 2025-05
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 61

Inclusion Criteria

• Provide written informed consent.
• 18 years old or older.
• Life expectancy of at least 12 weeks.
• Histologically- or cytologically-confirmed, advanced, metastatic, and/or progressive solid tumors for whom there is no authorized or effective therapy available, or for whom such therapies are considered inappropriate by the Investigator (in Part B, subjects with specific cancer types will be enrolled; Specific criteria will be introduced in a protocol amendment).
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

Part A

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Exclusion Criteria

• Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, or investigational agent within 28 days, (42 days for nitrosoureas, mitomycin-C) of first dose of NXP800. Subjects can continue to receive bisphosphonates due to metastatic bone disease or GnRH agonists if they have prostate cancer.
• Ongoing toxic manifestations of previous treatments > Grade 2.
• Subjects with treated brain metastases are eligible if there is no evidence of progression for at least 28 days after central nervous system (CNS) directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the Screening period.
• Female subjects who can become pregnant (or are already pregnant or lactating).
• Male subjects with partners of childbearing potential (unless they agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or to sexual abstinence).

Part B Inclusion Criteria:

• Provide written informed consent.

• 18 years old or older.

• Subjects with the following ARID1a mutated, ovarian/fallopian tube/primary peritoneal cancer histologies (ARID1a mutation status determined by a DNA-based Next Generation Sequencing test):

  • Clear cell ovarian carcinoma (≥ 50% clear cell carcinoma with no serous differentiation)
  • Endometrioid ovarian carcinoma

• Subjects must have disease progression within 6 months (182 days) from completion of platinum-based therapy (6 months should be calculated from the date of the last administered dose of platinum therapy to the date of radiographic imaging showing progression)

• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

• Subjects with a BRCA mutation must have received prior treatment with a PARP inhibitor.

• Subjects must have received at least 1 but not more than 3 prior systemic lines of anticancer therapy, including at least 1 line of therapy containing bevacizumab.

  • Adjuvant + neoadjuvant are considered one line of therapy
  • Maintenance therapy (i.e., bevacizumab, PARP inhibitors) will be considered as part of the preceeding line of therapy and are not counted independently.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Subjects must have a sufficient archival Formalin-Fixed Paraffin-Embedded (FFPE) tissue specimen, or be willing to consent to a fresh tissue biopsy during the study.

Part B Exclusion Criteria:

• Subjects with disease that did not respond to, or has progressed during or within 4 weeks of the last dose of first-line platinum containing chemotherapy.
• Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, or investigational agent within 28 days, (42 days for nitrosoureas, mitomycin-C) of first dose of NXP800.
• Ongoing toxic manifestations of previous treatments > Grade 2, with the exception of alopecia.
• Subjects with treated brain metastases are eligible if there is no evidence of progression for at least 12 weeks while off corticosteroids after central nervous system (CNS) directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the Screening period.
• Female subjects who can become pregnant (or are already pregnant or lactating).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A: Dose Escalation	NXP800	Escalating doses of NXP800 administered orally once or twice daily.
Part B: Expansion in Ovarian Cancers Cohort 1	NXP800	Subjects will be treated with NXP800 at 50 mg/day orally.
Part B: Expansion in Ovarian Cancers Cohort 2	NXP800	Subjects will be treated with NXP800 at 75 mg/day orally.

Primary Outcome Measures

Name	Time	Method
Part A: Number of patients with treatment related adverse events, clinical laboratory abnormalities, dose limiting toxicities	Day 28
Part B: Estimates of disease response by RECIST v 1.1	Baseline to 30 days post last dose of NXP800
Part B: Number of patients with treatment related adverse events, and/or clinical laboratory abnormalities.	Baseline to 30 days post last dose of NXP800

Secondary Outcome Measures

Name	Time	Method
Area under the concentration-time curve (AUC) of NXP800	First dose through Day 29
Maximum observed concentration (Cmax) of NXP800	First dose through Day 29
Time to peak concentration (Tmax) of NXP800	First dose through Day 29
Half-life (T1/2) of NXP800	First dose through Day 29

Trial Locations

Locations (23)

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Honor Health; 🇺🇸 Phoenix, Arizona, United States

UC San Diego Health - Moores Cancer Center; 🇺🇸 La Jolla, California, United States

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Yale Gynecologic Oncology; 🇺🇸 New Haven, Connecticut, United States

Florida Cancer Specialists South; 🇺🇸 Fort Myers, Florida, United States

Mount Sinai Comprehensive Cancer Center; 🇺🇸 Miami Beach, Florida, United States

Florida Cancer Specialists Research North; 🇺🇸 St. Petersburg, Florida, United States

Florida Cancer Specialists Research East; 🇺🇸 West Palm Beach, Florida, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Women's Cancer Care Associates; 🇺🇸 Albany, New York, United States

The Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

OU Health Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Oklahoma Cancer Specialists and Research Institute; 🇺🇸 Tulsa, Oklahoma, United States

Oncology Associates of Oregon; 🇺🇸 Eugene, Oregon, United States

Sidney Kimmel Cancer Center, Asplundh Cancer Pavilion; 🇺🇸 Willow Grove, Pennsylvania, United States

Texas Oncology; 🇺🇸 Fort Worth, Texas, United States

University of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States

VCU Massey Comprehensive Cancer Center; 🇺🇸 Richmond, Virginia, United States

Royal Marsden Hospital; 🇬🇧 London Borough of Sutton, Sutton Surrey, United Kingdom

Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

The Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom