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

Part A

Inclusion criteria

• Provide written informed consent.
• 18 years old or older.
• 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.
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Exclusion criteria

• Subjects with known human epidermal growth factor receptor 2 (HER2+) overexpressing malignancies.
• 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 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.
• 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 .
• 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).
• Major surgery from which the subject has not yet recovered.

Part B:

Inclusion criteria

• Provide written informed consent.
• 18 years old or older.
• Advanced, metastatic, and/or progressive solid tumors with pathogenic molecular alterations:

• Non-small cell lung cancer (adenocarcinoma); YES1, TYMS amplification or FAT1 pathogenic mutation
• Non-small cell lung cancer (squamous cell carcinoma); YES1, TYMS amplification or FAT1 pathogenic mutation
• Renal cancer; NF2 pathogenic mutation
• Mesothelioma; NF2 pathogenic mutation
• 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.
• Must have received 1-3 prior therapies appropriate for their tumor type and stage of disease
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (or mRECIST 1.1 for subjects with pleural mesothelioma).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Exclusion criteria

• Subjects with the following combination of cancer type and pathogenic molecular alterations are excluded:

• Subjects with colorectal cancer, glioma, melanoma, or anaplastic thyroid conditions with BRAF mutations.
• Subjects with NSCLC with BRAF or EGFR mutations or HER2 overexpression.
• 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) 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.
• Ongoing toxic manifestations of previous treatments > Grade 2 with the exception of alopecia and neuropathy.
• 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 .
• 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).
• Major surgery from which the subject has not yet recovered.