NXP800 for Advanced Cancers

Not currently recruiting at 25 trial locations

Overseen By Shay Shemesh, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nuvectis Pharma, Inc.

Must be taking: GnRH agonists, Bisphosphonates

Must not be taking: Nitrosoureas, Mitomycin-C

Disqualifiers: Pregnancy, 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: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests NXP800, a new treatment for advanced cancers, to assess its safety and effectiveness. Initially, it evaluates different doses for safety, then examines the treatment's efficacy in specific ovarian cancers with the ARID1a mutation. Individuals with these ovarian cancer types, whose disease has worsened after platinum-based therapy, might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

You may need to stop certain medications before joining the trial. Specifically, you cannot have had radiotherapy, endocrine therapy, chemotherapy, or investigational agents within 28 days (or 42 days for some specific drugs) before starting the trial. However, you can continue taking bisphosphonates for bone disease or GnRH agonists if you have prostate cancer.

Is there any evidence suggesting that NXP800 is likely to be safe for humans?

Research has shown that NXP800 has been administered to patients with recurrent ovarian cancer unresponsive to standard treatment. In one study, patients received 75 mg of NXP800 daily. The study found that most participants tolerated the treatment well. Side effects were typically mild to moderate, with common ones being nausea and tiredness, which were manageable and expected.

As a Phase 1 trial, the primary goal is to assess the safety of different doses. Results so far suggest that NXP800 is safe enough for further testing. However, as this is an early-stage trial, additional research is necessary to fully understand its long-term safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced cancers, such as chemotherapy and targeted therapies, NXP800 is being explored for its new approach. Researchers are excited because NXP800 offers a novel mechanism of action by targeting specific cancer pathways that are not addressed by current options. This oral treatment is designed to be taken once or twice daily, potentially providing a more convenient option for patients. With doses being tailored to specific needs during trials, NXP800 holds promise for being more effective and having fewer side effects compared to traditional therapies.

What evidence suggests that NXP800 might be an effective treatment for advanced cancers?

Studies have shown that NXP800 might help treat ovarian cancers with ARID1a mutations. In patients with these specific mutations, NXP800 led to one partial improvement and six cases where the disease remained stable. Lab tests on tumor samples also showed that it significantly slowed tumor growth. However, results are mixed, as other data suggest it might not always be effective. While there are hopeful signs, the treatment's success can vary. Participants in this trial will receive NXP800 in different dosages to further evaluate its effectiveness and safety. ^{1 2 6 7 8}

Who Is on the Research Team?

Susana Banerjee

Principal Investigator

Institute of Cancer Research, Royal Marsden NHS Foundation Trust

Udai Banerji, Prof

Principal Investigator

Institute of Cancer Research, Royal Marsden Foundation Trust

Are You a Good Fit for This Trial?

Adults with advanced solid tumors without effective treatment options, or those inappropriate as per the investigator. Specifically for Part B: adults with ARID1a mutated ovarian cancers who've had certain prior treatments and have measurable disease progression. Excludes pregnant/lactating women, men unwilling to prevent pregnancy, and those with recent other treatments or ongoing severe side effects.

Inclusion Criteria

You have a tumor that can be measured using the RECIST Version 1.1 guidelines.

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer worsened within 6 months after finishing platinum-based treatment.

Exclusion Criteria

I haven't had certain cancer treatments in the last 28-42 days.

I am a woman who could become pregnant, or am currently pregnant or breastfeeding.

I have severe side effects from past treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part A: Dose escalation by cohort to identify the maximum tolerated dose of NXP800 in patients with advanced cancers

8-12 weeks

Weekly visits for dose adjustments and monitoring

Expansion

Part B: Administration of selected doses to patients with platinum-resistant, ARID1a-mutated ovarian carcinoma

12 weeks

Bi-weekly visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• NXP800

Trial Overview NXP800 is being tested for safety at different doses/schedules in advanced cancer patients (Part A), and its preliminary efficacy in specific ovarian cancers with ARID1a mutation (Part B). The trial has two phases: dose escalation to assess safety and an expansion phase focusing on efficacy.

How Is the Trial Designed?

Group I: Part B: Expansion in Ovarian Cancers Cohort 2 Experimental Treatment 1 Intervention

Subjects will be treated with NXP800 at 75 mg/day orally.

Group II: Part B: Expansion in Ovarian Cancers Cohort 1 Experimental Treatment 1 Intervention

Subjects will be treated with NXP800 at 50 mg/day orally.

Group III: Part A: Dose Escalation Experimental Treatment 1 Intervention

Escalating doses of NXP800 administered orally once or twice daily.

NXP800 is already approved in United States for the following indications:

Approved in United States as NXP800 for:

• None approved; granted Fast Track and Orphan Drug Designation for ARID1a-deficient ovarian, fallopian tube, and peritoneal cancers, and Orphan Drug Designation for cholangiocarcinoma

Who Is Running the Clinical Trial?

Nuvectis Pharma, Inc.

Lead Sponsor

Trials

2

Recruited

100+

The European Network for Gynaecological Oncological Trial groups (ENGOT)

Collaborator

Trials

2

Recruited

870+

European Network for Gynaecological Oncological Trial Groups

Collaborator

Trials

4

Recruited

2,900+

Gynecologic Oncology Group Foundation

Collaborator

Trials

3

Recruited

1,300+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05226507

NCT05226507 | A Phase 1 Clinical Study of NXP800 in ... Part A of the study is a dose escalation by cohort study of NXP800 administered to patients with advanced cancers. The study will identify the maximum tolerated ...

2. firstwordpharma.com firstwordpharma.com/story/5985354

Nuvectis Pharma Provides Final Clinical Data Update from ... Overall, treatment resulted in 2 patients achieving partial response (unconfirmed) and 3 achieving stable disease. Thrombocytopenia, a key ...

3. fiercebiotech.com fiercebiotech.com/biotech/nuvectis-axes-ovarian-cancer-program-after-seeing-phase-1b-data

Nuvectis axes ovarian cancer program after seeing phase ... NXP800, a GCN2 kinase activator, has been on shaky ground since a data drop in November revealed a lack of efficacy. Seeking to improve outcomes ...

4. aacrjournals.org aacrjournals.org/mct/article/22/12_Supplement/B044/730625/Abstract-B044-Results-of-a-phase-1-dose-escalation

Results of a phase 1 dose escalation clinical trial of NXP800 ... In tumor samples from ARID1a-mutated ovarian carcinoma xenografts, treatment with NXP800 resulted in substantial tumor growth inhibition and ...

5. onclive.com onclive.com/view/nxp800-demonstrates-single-agent-activity-in-arid1a-platinum-resistant-ovarian-cancer

NXP800 Demonstrates Single-Agent Activity in ARID1a+ ... NXP800 demonstrated antitumor activity in platinum-resistant ovarian cancer with ARID1a mutations, with one partial response and six stable ...

6. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(24)00807-2/fulltext

A phase Ib, multicenter, open-label study of NXP800 ... The primary objective is to generate preliminary efficacy data and additional safety data among patients with ARID1A-mutated, platinum-resistant ovarian ...

7. targetedonc.com targetedonc.com/view/nxp800-gains-fda-orphan-drug-status-in-arid1a-deficient-ovarian-cancers

NXP800 Gains FDA Orphan Drug Status in ARID1a- ... NXP800 was granted orphan drug designation from the FDA in ARID1a-deficient ovarian, fallopian tube, and primary peritoneal cancers.

8. cancerresearchhorizons.com cancerresearchhorizons.com/news-and-events/our-news/nuvectis-pharma-announces-initiation-phase-1b-study-nxp800-platinum

Nuvectis Pharma announces initiation of the Phase 1b ... The Phase 1b study is a multicenter, single-agent, open-label clinical trial of NXP800 in patients with platinum-resistant, ARID1a-mutated ovarian cancer.