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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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. 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 or EGFR mutations or HER2 overexpression. 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

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Sequential assignment, dose escalation and expansion
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose Escalation (Part A) 		Escalating doses of NXP900 are planned with a starting dose level of 20 mg once per day.
  • Drug: NXP900
    NXP900 is an orally administered SRC/YES1 kinase inhibitor
Experimental
Dose Expansion (Part B) 		Participants will receive the selected dose of NXP900
  • Drug: NXP900
    NXP900 is an orally administered SRC/YES1 kinase inhibitor

Recruiting Locations

Mayo Clinic
Phoenix, Arizona 85054
Contact:
855-776-0015

UC San Diego Moores Cancer Center
La Jolla, California 92093

Sarah Cannon Research Institute at HealthONE
Denver, Colorado 80218
Contact:
720 754-2610

Mayo Clinic
Jacksonville, Florida 32224
Contact:
855-776-0015

University of Chicago
Chicago, Illinois 60637

Mayo Clinic Rochester
Rochester, Minnesota 55905

Memorial Sloan Kettering Cancer Center
New York, New York 10021

Cleveland Clinic
Cleveland, Ohio 44195

Oregon Health and Science University
Portland, Oregon 97239
Contact:
503-494-6865

The University of Texas MD Anderson Cancer Center
Houston, Texas 77030
Contact:
Jordi Rodon Ahnert, MD, PhD
713 792-5603

NEXT Oncology Houston
Houston, Texas 77054

NEXT Oncology Dallas
Irving, Texas 75039

NEXT Oncology Virginia
Fairfax, Virginia 22031

More Details

Status
Recruiting
Sponsor
Nuvectis Pharma, Inc.

Study Contact

Erin Belshaw
(201) 627-8129
ebelshaw@nuvectis.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.