NB003 for Solid Cancer

Recruiting at 74 trial locations

Overseen By Lanjiao Wu

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ningbo Newbay Technology Development Co., Ltd

Must not be taking: CYP3A4 inhibitors, acid-reducing agents

Disqualifiers: CNS metastases, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

258 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug, NB003 (also known as AZD3229), for individuals with advanced solid cancers, including specific genetic types of gastrointestinal stromal tumors (GIST) and other cancers with certain gene changes. It consists of two phases: one to determine the appropriate dose and another to further test that dose. Suitable candidates include those with advanced GIST or other solid cancers who have not responded to other treatments, especially if their cancer has specific genetic changes, such as KIT or PDGFRα mutations. Participants will take NB003 tablets twice daily in 28-day cycles. The trial aims to assess drug tolerance and behavior in the body. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you must stop any anti-cancer therapy at least 2 weeks before starting the study drug, and you cannot take medications that strongly affect the enzyme CYP3A4 or acid-reducing agents at least 2 weeks before the first dose.

Is there any evidence suggesting that NB003 is likely to be safe for humans?

Research has shown that NB003, a treatment under study for solid cancers, has undergone testing in earlier studies. NB003 was designed to target specific changes in cancer cells. In lab tests with mice, it demonstrated promising safety results, making it a candidate for human testing. As this trial is in the early phase, the primary goal is to ensure NB003's safety and to understand its mechanism in the body. Although detailed safety data from human studies is not yet available, the treatment's progression to this phase suggests it has shown some level of safety in earlier research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

NB003 is unique because it targets specific genomic alterations in cancers, like those found in GIST and other malignancies with KIT or PDGFRα mutations, which many standard treatments don't specifically address. Unlike traditional chemotherapy that broadly attacks dividing cells, NB003 works by honing in on these genetic changes, potentially offering a more tailored and effective approach. Additionally, NB003 is administered orally, which can be more convenient and less invasive than some existing cancer treatments that require intravenous delivery. Researchers are excited about its promise to improve outcomes by focusing on the genetic drivers of cancer.

What evidence suggests that NB003 might be an effective treatment for solid cancer?

Research has shown that NB003 may help treat certain solid cancers, particularly gastrointestinal stromal tumors (GIST). Earlier studies found NB003, which blocks certain proteins, to be generally safe. It also benefited GIST patients by extending periods without cancer progression and increasing rates of tumor shrinkage or disappearance. NB003 targets specific genetic changes often present in GIST and some other cancers. These early findings suggest that NB003 could be effective for cancers with these genetic changes. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors, particularly GIST or those with KIT/PDGFRα gene alterations who've exhausted standard treatments. They should have a life expectancy of at least 12 weeks, good performance status (able to carry out daily activities), and proper organ/marrow function. Can't join if they've had recent cancer therapy, major surgery, CNS metastases, active infections like hepatitis/HIV, severe diseases that could affect the trial's safety or results.

Inclusion Criteria

I have provided a sample of my tumor for testing.

For dose escalation phase: GIST patients must have progressed on or had an intolerability to imatinib and other SoCs or refused other SoCs. Patients with an advanced solid tumor other than GIST must have relapsed or had refractory disease without an available effective therapy and harbor KIT or PDGFRα gene alterations (central laboratory confirmation is not required for screening). For dose expansion phase: Cohort 1: GIST patients with KIT or PDGFRα gene mutations, must have progressed on or been intolerant to at least imatinib, sunitinib, regorafenib and ripretinib (≥ fifth line therapy setting); Cohort 2a: GIST patients with KIT or PDGFRα gene mutations, must have progressed on or been intolerant to imatinib and sunitinib, and who have not received additional systemic therapy for advanced GIST (third line therapy setting); Cohort 2b: GIST patients with KIT or PDGFRα gene mutations, must have progressed on or been intolerant to imatinib, sunitinib and regorafenib, and who have not received additional systemic therapy for advanced GIST (forth line therapy setting); Cohort 3: GIST patients with KIT or PDGFRα gene mutations, must have progressed on or been intolerant to imatinib and have not received additional systemic therapy for advanced GIST (second line therapy setting); Cohort 4: GIST patients with PDGFRα exon 18 mutation and must have progressed on or been intolerant to avapritinib; in the countries/regions where avapritinib is not SoC, avapritinib-naïve patients can be enrolled; Cohort 5: Unresectable or metastatic melanoma patients with demonstrated evidence for KIT gene mutation and/or amplification, must have progressed on or been intolerant to SoCs; Cohort 6: Patients with other advanced malignancies other than GIST or melanoma which must be relapsed or refractory without an available effective therapy and harbor KIT or PDGFRα gene alterations. For dose expansion phase: at least one measurable lesion per RECIST v1.1/mRECIST

Life expectancy ≥ 12 weeks

Exclusion Criteria

I received targeted radiation for symptom relief within the last week.

I have not had major surgery in the last 4 weeks.

Any evidence of severe or uncontrolled systemic diseases which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive NB003 tablets orally twice daily for repeated 28-day cycles to determine the MTD or MAD and RP2D

Approximately 24 months

Regular visits as per protocol

Dose Expansion

Additional patients are enrolled at RP2D to further explore safety, tolerability, PK, efficacy, and biological activity of NB003

Approximately 26 months

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NB003

Trial Overview The study is testing NB003 tablets on patients with advanced malignancies to evaluate their safety and how the body processes them. It's an early-phase trial (Phase 1) where everyone gets NB003; there are no comparison groups. The trial has two parts: dose escalation to find the right dose and expansion to test it further in specific patient groups.

How Is the Trial Designed?

Group I: Dose Escalation Phase and Dose Expansion Phase Experimental Treatment 1 Intervention

Dose escalation cohort: NB003 tablets will be administered orally twice daily for repeated 28-day cycles until discontinuation criteria are met. RP2D: one or more putative RP2D(s) will be explored in dose escalation phase with approximately 15 patients for each provisional RP2D(s) Dose expansion phase: In the dose expansion phase, additional patients will be enrolled at RP2D to further explore the safety, tolerability, PK, efficacy and biological activity of NB003 in specific disease cohorts, including GIST and other malignancies harboring genomic alterations of KIT or PDGFRα.

Who Is Running the Clinical Trial?

Ningbo Newbay Technology Development Co., Ltd

Lead Sponsor

Trials

2

Recruited

380+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.11517

The broad-spectrum KIT inhibitor NB003 and activity in ... Conclusions: NB003 demonstrated a manageable safety profile, and showed encouraging clinical benefit in GIST pts, as evidenced by mPFS and cORR, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10400151/

Molecular Advances in the Treatment of ... NB003 (Previously AZD3229: Ningbo Newbay Technology Development Co., Ltd), was also designed as a broad inhibitor of KIT and PDGFRA mutant GIST.

3. science.org science.org/doi/10.1126/scitranslmed.aaz2481

Discovery and pharmacological characterization of ... Gastrointestinal stromal tumor (GIST) is the most common human sarcoma driven by mutations in KIT or platelet-derived growth factor α (PDGFRα).

4. ascopubs.org ascopubs.org/doi/pdfdirect/10.1200/JCO.2025.43.16_suppl.11517

The broad-spectrum KIT inhibitor NB003 and activity in ... Conclusions: NB003 demonstrated a manageable safety profile, and showed encouraging clinical benefit in GIST pts, as evidenced by mPFS and cORR, across multiple ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9471148/

An overview of agents and treatments for PDGFRA-mutated ... In this study, only 12 patients (5%) had a PDGFRA mutation, thus, the available data is too limited to draw conclusions on the efficacy of sunitinib on survival ...

6. gisttrials.org gisttrials.org/iLRG/details.php?Trial=377

A Study of NB003 in Patients With Advanced Malignancies This is a phase 1, open-label, multicenter study of NB003 which comprised of a dose escalation phase to determine the MTD or maximum administered dose (MAD) ...