NXP900 for Advanced Cancers

Recruiting at 7 trial locations

Overseen By Shay Shemesh

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nuvectis Pharma, Inc.

Must be taking: Bisphosphonates, GnRH agonists

Must not be taking: Chemotherapy, Radiotherapy

Disqualifiers: HER2+ malignancies, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called NXP900 to see how safe it is for people with advanced cancers. Researchers are trying different doses to find out which one works best without causing too many side effects. The goal is to determine the best dose for future studies.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have had radiotherapy, chemotherapy, or certain other treatments within 28 days before starting the trial. You can continue taking bisphosphonates for bone disease or GnRH agonists for prostate cancer.

What makes the drug NXP900 unique for treating advanced cancers?

NXP900, also known as eCF506, is unique because it targets heat shock protein 90 (HSP90), a protein that helps cancer cells survive and grow. By inhibiting HSP90, NXP900 disrupts multiple pathways that cancer cells use to thrive, making it a novel approach compared to traditional treatments that often target only one pathway. ^{1 2 3 4 5}

Research Team

Udai Banerji, Prof

Principal Investigator

Institute of Cancer Research, Royal Marsden NHS Foundation Trust

Eligibility Criteria

This trial is for adults with advanced solid tumors that have no effective therapy options or where such treatments are not suitable. Participants must be able to measure their disease, have a good performance status (ECOG 0-1), and agree to use contraception if they can become pregnant. Those with certain types of cancer, recent other treatments, untreated brain metastases, or unresolved major surgery side effects cannot join.

Inclusion Criteria

Provide written informed consent

I am 18 years old or older.

Have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Exclusion Criteria

I am still recovering from a major surgery.

I haven't had cancer treatment, except for bone disease or prostate cancer therapy, in the last 28 days.

I am a man and will use a condom and spermicide if my partner can have children.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of NXP900 starting at 20 mg once per day

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• NXP900

Trial Overview The study is testing different doses and schedules of a new drug called NXP900 on patients with various advanced cancers. It's an early-stage trial (Phase 1) focused on finding out the safest dose levels and how often the drug should be given.

Participant Groups

Group I: Dose Escalation Experimental Treatment 1 Intervention

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

NXP900 is already approved in United States for the following indications:

Approved in United States as NXP900 for:

• None approved; currently in Phase 1 clinical trials

Who Is Running the Clinical Trial?

Nuvectis Pharma, Inc.

Lead Sponsor

Trials

2

Recruited

100+

Findings from Research

The study found that ECT2 is a key factor in the growth of triple-negative breast cancer (TNBC) cells, influencing their proliferation, invasion, and apoptosis, as demonstrated through in vitro assays with the HCC1806 cell line.

Silencing ECT2 significantly enhanced the effectiveness of paclitaxel (PTX) treatment in TNBC, suggesting that targeting ECT2 could be a promising strategy to improve breast cancer therapies and potentially lead to the development of new targeted treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Ect2 Expression on the Growth of Triple-Negative Breast Cancer Cells with Paclitaxel Intervention. Wang, H., Liu, H., Li, J., et al.[2022]

Extracellular heat-shock protein 90 (eHsp90) plays a significant role in promoting cancer stem-like characteristics in prostate cancer cells, enhancing their self-renewal and growth, which could contribute to tumor progression.

eHsp90 is associated with increased expression of stem-like markers and the epithelial to mesenchymal transition (EMT) factor Snail, suggesting it may help create a unique population of cancer stem cells that are more resistant to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secreted heat shock protein 90 promotes prostate cancer stem cell heterogeneity. Nolan, KD., Kaur, J., Isaacs, JS.[2023]

GPNMB is a marker indicating poor prognosis in triple-negative breast cancer (TNBC), and its levels can increase in response to various cancer therapies, which may affect the efficacy of the drug Glembatumumab Vedotin.

Inhibiting heat shock protein 90 (HSP90) enhances both the expression and surface localization of GPNMB, making breast cancer cells more sensitive to Glembatumumab Vedotin, suggesting that combining HSP90 inhibitors with this drug could improve treatment outcomes for metastatic TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HSP90 inhibitors induce GPNMB cell-surface expression by modulating lysosomal positioning and sensitize breast cancer cells to glembatumumab vedotin. Biondini, M., Kiepas, A., El-Houjeiri, L., et al.[2022]

In a phase III trial involving 677 patients with advanced lung adenocarcinoma, the combination of ganetespib and docetaxel did not improve overall survival compared to docetaxel alone, with median survival times of 10.9 months versus 10.5 months, respectively.

The addition of ganetespib also did not enhance progression-free survival or any secondary outcomes, and the most common serious side effect was neutropenia, occurring in 30.9% of patients receiving the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase III Study of Ganetespib, a Heat Shock Protein 90 Inhibitor, With Docetaxel Versus Docetaxel in Advanced Non-Small-Cell Lung Cancer (GALAXY-2). Pillai, RN., Fennell, DA., Kovcin, V., et al.[2020]

The HSP90 inhibitor NVP-AUY922 effectively inhibited the growth of oral squamous cell carcinoma cells in laboratory studies and induced apoptosis, suggesting it can be a powerful treatment option.

In animal models, NVP-AUY922 demonstrated significant antitumor effects by degrading key oncoproteins and reducing factors like p-Akt and VEGF, which are involved in tumor progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma. Okui, T., Shimo, T., Hassan, NM., et al.[2014]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Effect of Ect2 Expression on the Growth of Triple-Negative Breast Cancer Cells with Paclitaxel Intervention. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Secreted heat shock protein 90 promotes prostate cancer stem cell heterogeneity. [2023]

3. England pubmed.ncbi.nlm.nih.gov

HSP90 inhibitors induce GPNMB cell-surface expression by modulating lysosomal positioning and sensitize breast cancer cells to glembatumumab vedotin. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Randomized Phase III Study of Ganetespib, a Heat Shock Protein 90 Inhibitor, With Docetaxel Versus Docetaxel in Advanced Non-Small-Cell Lung Cancer (GALAXY-2). [2020]

5. Greece pubmed.ncbi.nlm.nih.gov

Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma. [2014]