Advanced Solid Tumor, Mesothelioma, Non-small Cell Lung Adenocarcinoma, Non-Small Cell Squamous Lung Cancer, NSCLC (Non-small Cell Lung Cancer), Renal Cancer
Conditions
Keywords
Solid Tumor, Carcinoma, Neoplasms, Adenocarcinoma, YES1, YAP1, TAZ1, NF2, FAT1, LATS1, TYMS, gene amplification, gene mutation, IDH1, IDH2
Brief summary
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.
Interventions
DRUGNXP900
NXP900 is an orally administered SRC/YES1 kinase inhibitor
Sponsors
Nuvectis Pharma, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Sequential assignment, dose escalation and expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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, or TAZ1 gene amplification, or cholangiocarcinoma with IDH1 or IDH2 mutations. 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 (or mRECIST 1.1 for subjects with pleural mesothelioma). 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Best response of complete response (CR) or partial response (PR) per RECIST 1.1 (or mRECIST 1.1 for subjects with pleural mesothelioma). |
| Part B: Duration of Response (DoR) | Up to 24 months | Confirmed CR or PR from the first documented response to the date of documented disease progression or death. |
| Part B: Disease Control Rate (DCR) | Up to 24 months | The proportion of patients with stable disease (SD), partial response (PR), or complete response (CR). |
Secondary
| Measure | Time frame |
|---|---|
| Area under the concentration-time curve (AUC) of NXP900 | Up to 24 months |
| Maximum observed concentration (Cmax) of NXP900 | Up to 24 months |
| Time to peak concentration (Tmax) of NXP900 | Up to 24 months |
| Half-life (T1/2) of NXP900 | Up to 24 months |
| Apparent volume of distribution at steady state (Vss/F) of NXP900 | Up to 24 months |
| Apparent plasma clearance at steady state (Clss/F) of NXP900 | Up to 24 months |
Countries
United Kingdom, United States
Contacts
CONTACTErin Belshaw
CONTACTShay Shemesh
PRINCIPAL_INVESTIGATORUdai Banerji, Prof
Institute of Cancer Research, Royal Marsden NHS Foundation Trust
PRINCIPAL_INVESTIGATORGerald Falchook, MD
Sarah Cannon Cancer Institute, HealthOne Denver
Outcome results
None listed