RecruitingPhase 1NCT05873686

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


Sponsor

Nuvectis Pharma, Inc.

Enrollment

140 participants

Start Date

Oct 26, 2023

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria17

  • Part A
  • Provide written informed consent.
  • 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.
  • Provide written informed consent.
  • 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, TAZ1 gene amplification
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Exclusion Criteria18

  • 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:
  • 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, EGFR or HER2 alterations.
  • 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.

Interventions

DRUGNXP900

NXP900 is an orally administered SRC/YES1 kinase inhibitor


Locations(12)

Mayo Clinic

Phoenix, Arizona, United States

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Mayo Clinic

Jacksonville, Florida, United States

University of Chicago

Chicago, Illinois, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Oregon Health and Science University

Portland, Oregon, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

NEXT Oncology Houston

Houston, Texas, United States

NEXT Oncology Dallas

Irving, Texas, United States

NEXT Oncology Virginia

Fairfax, Virginia, United States

Western General Hospital - NHS Lothian

Edinburgh, United Kingdom

The Royal Marsden NHS Foundation and Trust

London, United Kingdom

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NCT05873686


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