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A Phase 1 Clinical Study of NXP900 in Subjects With Advanced Cancers

NCT05873686 · Nuvectis Pharma, Inc.
In plain English

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About this study
This is a multi-center, first-in-human, open label, dose escalation (Part A) and expansion (Part B) Phase 1 study in subjects with advanced solid tumors and in subjects with solid tumors with selected genetic alterations that are either direct (YES1 amplification) or dependent (Hippo Pathway alterations) targets of NXP900.
Eligibility criteria
Part A Inclusion Criteria: 1. Provide written informed consent. 2. 18 years old or older. 3. 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. 4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Exclusion Criteria: 1. Subjects with known human epidermal growth factor receptor 2 (HER2+) overexpressing malignancies. 2. Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, or investigational agent within 28 days, (42 days for nitrosoureas, mitomycin-C) of first dose of NXP900. Subjects can continue to receive bisphosphonates due to metastatic bone disease or GnRH agonists if they have prostate cancer. 3. Ongoing toxic manifestations of previous treatments \> Grade 2 with the exception of alopecia and neuropathy. 4. Subjects with treated brain metastases with evidence of progression within 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. 5. Female subjects who can become pregnant (or are already pregnant or lactating), unless they have a negative serum pregnancy test before enrollment and agree to use at least one highly effective form of contraception . 6. 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). 7. Major surgery from which the subject has not yet recovered. Part B: Inclusion Criteria: 1. Provide written informed consent. 2. 18 years old or older. 3. Advanced, metastatic, and/or progressive solid tumors with pathogenic molecular alterations: 1. Non-small cell lung cancer (adenocarcinoma); YES1, TYMS amplification or FAT1 pathogenic mutation 2. Non-small cell lung cancer (squamous cell carcinoma); YES1, TYMS amplification or FAT1 pathogenic mutation 3. Renal cancer; NF2 pathogenic mutation 4. Mesothelioma; NF2 pathogenic mutation 5. Other solid tumors with a NF2, FAT1 or LATS1 pathogenic gene mutation or TYMS, YAP1, YES1, TAZ1 gene amplification 4. Must have received 1-3 prior therapies appropriate for their tumor type and stage of disease 5. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Exclusion Criteria: 1. Subjects with the following combination of cancer type and pathogenic molecular alterations are excluded: 1. Subjects with colorectal cancer, glioma, melanoma, or anaplastic thyroid conditions with BRAF mutations. 2. Subjects with NSCLC with BRAF, EGFR or HER2 alterations. 3. Subjects with breast cancer, gastric cancer, esophageal junction adenocarcinoma or biliary cancer with HER2 alterations, 2. Subjects with anal, penile, cervical or head and neck cancers with a prior history of human papilloma virus (HPV) infection. 3. Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, or investigational agent within 28 days (42 days for nitrosoureas, mitomycin-C) prior to first dose of NXP900. Subjects can continue to receive bisphosphonates due to metastatic bone disease or GnRH agonists if they have prostate cancer. 4. Ongoing toxic manifestations of previous treatments \> Grade 2 with the exception of alopecia and neuropathy. 5. Female subjects who can become pregnant (or are already pregnant or lactating), unless they have a negative serum pregnancy test before enrollment and agree to use at least one highly effective form of contraception . 6. 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). 7. Major surgery from which the subject has not yet recovered.
Study design
Enrollment target: 140 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2023-10-26
Estimated completion: 2027-07
Last updated: 2026-03-03
Interventions
Drug: NXP900
Primary outcomes
  • Number of patients with treatment related adverse events and/or clinical laboratory abnormalities (Up to 30 days post treatment)
  • Part A: Number of patients who experience Dose Limiting Toxicities (DLT) as defined in the protocol (Day 28)
  • Part B: Objective response rate (ORR) (Up to 24 months)
Sponsor
Nuvectis Pharma, Inc. · industry
Contacts & investigators
ContactErin Belshaw · contact · ebelshaw@nuvectis.com · (201) 627-8129
ContactShay Shemesh · contact · sshemesh@nuvectis.com · (201) 614-3153
InvestigatorUdai Banerji, Prof · principal_investigator, Institute of Cancer Research, Royal Marsden NHS Foundation Trust
InvestigatorGerald Falchook, MD · principal_investigator, Sarah Cannon Cancer Institute, HealthOne Denver
All locations (12)
Mayo ClinicRecruiting
Phoenix, Arizona, United States
Sarah Cannon Research Institute at HealthONERecruiting
Denver, Colorado, United States
Mayo ClinicRecruiting
Jacksonville, Florida, United States
University of ChicagoRecruiting
Chicago, Illinois, United States
Mayo Clinic RochesterRecruiting
Rochester, Minnesota, United States
Oregon Health and Science UniversityRecruiting
Portland, Oregon, United States
The University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
NEXT Oncology HoustonRecruiting
Houston, Texas, United States
NEXT Oncology DallasRecruiting
Irving, Texas, United States
NEXT Oncology VirginiaRecruiting
Fairfax, Virginia, United States
Western General Hospital - NHS LothianCompleted
Edinburgh, United Kingdom
The Royal Marsden NHS Foundation and TrustCompleted
London, United Kingdom
A Phase 1 Clinical Study of NXP900 in Subjects With Advanced Cancers · TrialPath