IRB Study Number 25-872
Status Recruiting
Location Cleveland Clinic Main Campus
Institute Taussig Cancer Institute
Description
Primary Objectives:
To generate preliminary efficacy data and additional safety data in subjects with advanced solid tumors, including NSCLC, mesothelioma, renal cancer and other solid tumors harboring NF2, FAT1 or LATS1 gene mutations or TYMS, YES1, YAP1 or TAZ1 gene amplifications.
Secondary Objectives:
To further characterize the PK profile of NXP900.
Exploratory Objectives:
To describe the treatment effect of NXP900 on pharmacodynamic markers.
Inclusion Criteria
Subjects must meet all of the following criteria to be eligible for study participation:
- Provide written informed consent.
- 18 years old or older.
- Eligible subjects include:
a. Subjects with unresectable, locally advanced or metastatic malignancies with pathogenic molecular alterations identified through ctDNA or next generation sequencing (NGS) performed using an FDA approved/CE marked commercially available test or by a CLIA or ISO 15189 certified laboratory, including:
i. Non-small cell lung cancer (adenocarcinoma); YES1, TYMS amplification or FAT1 pathogenic mutation
ii. Non-small cell lung cancer (squamous cell carcinoma); YES1, TYMS amplification or FAT1 pathogenic mutation
iii. Renal cancer; NF2 pathogenic mutation
iv. Mesothelioma; NF2 pathogenic mutation
v. Other solid tumors with a NF2, FAT1 or LATS1 pathogenic gene mutation or TYMS, YAP1, YES1, TAZ1 gene amplification.
b. Subjects must have received 1-3 prior therapies appropriate for their tumor type and stage of disease, including targeted therapies and/or immunotherapy, if applicable, in the recurrent setting. Subjects with >3 prior treatment regimens may be considered after discussion with the Sponsor. - Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Hematological and biochemical indices within the ranges shown below.
a. Hemoglobin: ≥ 9.0 g/dL or ≥ 10.0 g/L if transfusion within last 4 weeks.
b. Absolute neutrophil count: ≥ 1.5×109/L.
c. Platelet count: ≥ 100×109/L.
d. Bilirubin: ≤1.5× the upper limit of normal (ULN), unless raised due to Gilbert’s syndrome in which case direct (not total) bilirubin will be used.
e. Alanine and aspartate aminotransferase (ALT and AST): ≤ ×2.5 ULN unless raised due to tumor, in which case ≤5×ULN is permissible.
f. Calculated creatinine clearance (using the Cockcroft & Gault formula): >45 mL/min (uncorrected value).
Exclusion Criteria
Subjects meeting any of the following criteria are not eligible for study participation:
- Subjects with the following combination of cancer type and pathogenic molecular alterations are excluded:
a. Subjects with colorectal cancer, glioma, melanoma, or anaplastic thyroid conditions with BRAF mutations.
b. Subjects with NSCLC with BRAF, EGFR or HER2 alterations.
c. Subjects with breast cancer, gastric cancer, esophageal junction adenocarcinoma or biliary cancer with HER2 alterations. - Subjects with anal, penile, cervical or head and neck cancers with a prior history of human papilloma virus (HPV) infection.
- 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.
- Ongoing toxic manifestations of previous treatments > Grade 2 with the exception of alopecia and neuropathy.
- 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). However, female subjects who have a negative serum or urine pregnancy test before enrollment and agree to use at least one highly effective form of contraception (such methods include: combined [estrogen and progestin containing] hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); Intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomized partner [provided that partner is the sole sexual partner of the female study participant and that the vasectomized partner has received medical assessment of the surgical success]) or agree to sexual abstinence, effective from the first administration of NXP900, throughout the study and for 6 months afterwards can be eligible. (Note: abstinence is only considered to be an acceptable method of contraception when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
- 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 (see note in Exclusion Criterion 7) effective from the first administration of NXP900, throughout the study and for 6 months afterwards. Men with partners of childbearing potential must also be willing to advise their partner to use an effective method of contraception for the same duration (for example, hormonal contraception, intra-uterine device, diaphragm with spermicidal gel or sexual abstinence). Men with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure of the foetus or neonate.
- Major surgery from which the subject has not yet recovered.
- At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
- Known to be serologically positive for hepatitis B, hepatitis C or Human immunodeficiency virus (HIV).
- Subjects with severe cardiovascular abnormalities, including but not limited to, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, recent myocardial infarction.
- QT/QTc interval > 470 ms using Fredericia’s QT correction formula.
- Subjects with known hypersensitivity to sorbitol or any components of NXP900.
- Any other condition which would not make the subject a good candidate for the clinical study in the opinion of the Investigator.
