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

NCT05873686 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NXP900-101
• Study Type: interventional
• Target: 140
• Locations: 2 countries
• Sites: 12

Brief 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.

Conditions

Advanced Solid Tumor; Renal Cancer; NSCLC (Non-small Cell Lung Cancer); Mesothelioma; Non-Small Cell Squamous Lung Cancer; Non-small Cell Lung Adenocarcinoma

Keywords

Solid Tumor; Carcinoma; Neoplasms; Adenocarcinoma; YES1; YAP1; TAZ1; NF2; FAT1; LATS1; TYMS; gene amplification; gene mutation

Outcome Measures

Primary Outcomes (5)

• 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

  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 Outcomes (6)

• 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

Study Arms (2)

Dose Escalation (Part A)

EXPERIMENTAL

Escalating doses of NXP900 are planned with a starting dose level of 20 mg once per day.

Drug: NXP900

Dose Expansion (Part B)

EXPERIMENTAL

Participants will receive the selected dose of NXP900

Drug: NXP900

Interventions

NXP900 DRUG

NXP900 is an orally administered SRC/YES1 kinase inhibitor

Dose Escalation (Part A); Dose Expansion (Part B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Nuvectis Pharma, Inc.: lead

Study Sites (12)

Mayo Clinic

Phoenix, Arizona, 85054, United States

RECRUITING

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology Houston

Houston, Texas, 77054, United States

RECRUITING

NEXT Oncology Dallas

Irving, Texas, 75039, United States

RECRUITING

NEXT Oncology Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Western General Hospital - NHS Lothian

Edinburgh, EH4 2XU, United Kingdom

COMPLETED

The Royal Marsden NHS Foundation and Trust

London, SW3 6JJ, United Kingdom

COMPLETED

Related Publications (1)

• 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.

  PMID: 39089584 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Kidney Neoplasms; Mesothelioma; Carcinoma; Neoplasms; Adenocarcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial

Study Officials

• Udai Banerji, Prof

  Institute of Cancer Research, Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Gerald Falchook, MD

  Sarah Cannon Cancer Institute, HealthOne Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erin Belshaw

CONTACT

(201) 627-8129; ebelshaw@nuvectis.com

Shay Shemesh

CONTACT

(201) 614-3153; sshemesh@nuvectis.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential assignment, dose escalation and expansion

Study Record Dates

• First Submitted: May 15, 2023
• First Posted: May 24, 2023
• Study Start: October 26, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); GB (2)