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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Mesothelioma; Advanced Solid Tumor; Renal Cancer; Non-Small Cell Squamous Lung Cancer; NSCLC (Non-small Cell Lung Cancer); Non-small Cell Lung Adenocarcinoma
• Intervention / Treatment: Drug: NXP900

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital - NHS Lothian
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation and Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • Houston, Texas, United States, 77054
      • NEXT Oncology Houston
    • Irving, Texas, United States, 75039
      • NEXT Oncology Dallas
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Oncology Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Best response of complete response (CR) or partial response (PR) per RECIST 1.1 (or mRECIST 1.1 for subjects with pleural mesothelioma).	Up to 24 months
Part B: Duration of Response (DoR)	Confirmed CR or PR from the first documented response to the date of documented disease progression or death.	Up to 24 months
Part B: Disease Control Rate (DCR)	The proportion of patients with stable disease (SD), partial response (PR), or complete response (CR).	Up to 24 months

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Nuvectis Pharma, Inc.
• Investigators: Principal Investigator: Udai Banerji, Prof, Institute of Cancer Research, Royal Marsden NHS Foundation Trust; Principal Investigator: Gerald Falchook, MD, Sarah Cannon Cancer Institute, HealthOne Denver

Publications and helpful links

General Publications

• Dash S, Hanson S, King B, Nyswaner K, Foss K, Tesi N, Harvey MJB, Navarro-Marchal SA, Woods A, Poradosu E, Unciti-Broceta A, Carragher NO, Brognard J. The SRC family kinase inhibitor NXP900 demonstrates potent antitumor activity in squamous cell carcinomas. J Biol Chem. 2024 Sep;300(9):107615. doi: 10.1016/j.jbc.2024.107615. Epub 2024 Jul 31.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: May 15, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): September 30, 2026
• Last Update Submitted That Met QC Criteria: September 25, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Carcinoma; Neoplasms; Adenocarcinoma; Solid Tumor; IDH1; IDH2; NF2; gene mutation; YAP1; FAT1; YES1; TAZ1; LATS1; TYMS; gene amplification
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Urologic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Carcinoma; Mesothelioma; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Kidney Neoplasms
• Other Study ID Numbers: NXP900-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No