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

Nuvectis Pharma

Status and phase: Enrolling; Phase 1

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

Treatments: Drug: NXP900

Study type: Interventional

Funder types: Industry

Identifiers

NCT05873686

NXP900-101

Details and patient eligibility

About

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.

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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, TAZ1 gene amplification

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.

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, EGFR or HER2 alterations.
   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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

Dose Escalation (Part A)

Experimental group

Description:

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

Treatment:

Drug: NXP900

Dose Expansion (Part B)

Experimental group

Description:

Participants will receive the selected dose of NXP900

Treatment:

Drug: NXP900