Clinical trial NCT05226507: A Phase 1 Clinical Study of NXP800 in Subjects with Advanced Cancers and Expansion in Subjects with Ovarian Cancer
Official title: A Phase 1 Clinical Study of NXP800 in Subjects with Advanced Cancers and Expansion in Subjects with Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Ovarian Cancer
Ovarian Clear Cell Carcinoma
Ovarian Clear Cell Tumor
Ovarian Clear Cell Adenocarcinoma
Ovarian Endometrioid Adenocarcinoma
Ovarian Endometrioid Tumor
ARID1A Gene Mutation
Keywords: Solid Tumor
Carcinoma
Neoplasms
Adenocarcinoma
ARID1a
Lead sponsor: Nuvectis Pharma, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Gynecologic Oncology Group Foundation
name: The European Network for Gynaecological Oncological Trial groups (ENGOT)
First posted: 2022-02-07
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part A dose escalation followed by Part B, expansion in ovarian cancers.
Primary purpose: TREATMENT

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.

Eligibility criteria: Part A 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 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).

Primary outcomes:
measure: Part A: Number of patients with treatment related adverse events, clinical laboratory abnormalities, dose limiting toxicities
timeFrame: Day 28
measure: Part B: Estimates of disease response by RECIST v 1.1
timeFrame: Baseline to 30 days post last dose of NXP800
measure: Part B: Number of patients with treatment related adverse events, and/or clinical laboratory abnormalities.
timeFrame: Baseline to 30 days post last dose of NXP800
Secondary outcomes:
measure: Area under the concentration-time curve (AUC) of NXP800
timeFrame: First dose through Day 29
measure: Maximum observed concentration (Cmax) of NXP800
timeFrame: First dose through Day 29
measure: Time to peak concentration (Tmax) of NXP800
timeFrame: First dose through Day 29
measure: Half-life (T1/2) of NXP800
timeFrame: First dose through Day 29
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Honor Health
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Health - Moores Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale Gynecologic Oncology
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists South
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: St. Petersburg
country: United States
facility: Florida Cancer Specialists Research North
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists Research East
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albany
country: United States
facility: Women's Cancer Care Associates
state: New York
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute
state: Oklahoma
city: Eugene
country: United States
facility: Oncology Associates of Oregon
state: Oregon
city: Willow Grove
country: United States
facility: Sidney Kimmel Cancer Center, Asplundh Cancer Pavilion
state: Pennsylvania
city: Fort Worth
country: United States
facility: Texas Oncology
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Richmond
country: United States
facility: VCU Massey Comprehensive Cancer Center
state: Virginia
city: London Borough of Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Sutton Surrey
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
Study officials:
affiliation: Institute of Cancer Research, Royal Marsden Foundation Trust
name: Udai Banerji, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Cancer Research, Royal Marsden NHS Foundation Trust
name: Susana Banerjee, Dr
role: PRINCIPAL_INVESTIGATOR
References: