A Study of NB003 in Patients With Advanced Malignancies

NCT04936178 | Completed Phase 1 FDA Drug

• 1 other identifier: NB003-01
• Study Type: interventional
• Target: 258
• Locations: 6 countries
• Sites: 32

Brief Summary

This a A Phase 1, Open-label, Multicenter Study to Assess the Safety, Tolerability, and Pharmacokinetics of NB003 in Subjects with Advanced Malignancies

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Incidence of dose-limiting toxicities

  Dose Escalation Phase：Dose-limiting toxicities will be reviewed as a subset of adverse events that occur within the first 28 days of dosing and meet protocol-specified criteria.

  Approximately 24 months since the escalation first subject enrolled

• Incidence of adverse events

  Dose Escalation Phase and Dose Expansion Phase: An AE is any untoward medical occurrence in a participant who received study drug without regard to causal relationship.

  Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled

• Objective Response Rate (ORR)

  Dose Expansion Phase: Objective Response Rate (ORR) which is defined as the percentage of patients whose efficacy is confirmed as complete response(CR) or partial responses(PR)

  Approximately 26 months since the Expansion first subject enrolled

• Duration of Response(DOR)

  Dose Expansion Phase: DOR is defined as the time from the date of first documented response until date of documented progression, for subjects who achieve CR or PR.

  Approximately 26 months since the Expansion first subject enrolled.

Secondary Outcomes (6)

• Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t)

  Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled

• Maximum observed plasma concentration (Cmax)

  Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled

• Time to Cmax (Tmax)

  Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled

• Terminal elimination half life

  Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled

• Objective Response Rate (ORR)

  Approximately 24 months since the escalation first subject enrolled

Other Outcomes (1)

• Cancer relevant gene mutations

  Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled

Study Arms (1)

Dose Escalation Phase and Dose Expansion Phase

EXPERIMENTAL

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.

Drug: NB003 tablets

Interventions

NB003 tablets DRUG

NB003 tablets will be administered at assigned doses for escalation phase and RP2D doses for expansion phase orally twice daily for repeated 28-day cycles until discontinuation criteria are met.

Dose Escalation Phase and Dose Expansion Phase

Eligibility Criteria

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

You may qualify if:

• Males or females of any race ≥18 years age.
• Histologically-confirmed diagnosis of unresectable, relapsed or metastatic GIST or other advanced malignancies.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 12 weeks.
• Adequate organ and marrow function.
• Tumor sample collection is required.

You may not qualify if:

• Prior anti-cancer therapy within 2 weeks or at least 5 half-lives, whichever is longer, up to a maximum wash-out period of 21 days prior to the initiation of study drug administration.
• Major surgery within 4 weeks of the first dose.
• Radiotherapy with a limited field of radiation for palliation within 1 week prior to the first dose, with the exception as defined.
• Patients currently receiving medications or herbal supplements known to be strong inhibitors or inducers of CYP3A4.
• Patients currently receiving acid-reducing agents and are unable to stop use at least 2 weeks prior to the first dose.
• Any known active central nervous system metastases and/or carcinomatous meningitis. Active infection including hepatitis B, hepatitis C, and HIV.
• Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, uncontrolled pericardial effusion, uncontrolled pleural effusion, or any other conditions, which in the judgment of Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks.
• 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.

Sponsors & Collaborators

• Ningbo Newbay Technology Development Co., Ltd: lead

Study Sites (32)

Standford University

Stanford, California, 32224, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

Long Island City, New York, 11101, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

U T MD Anderson Cancer Center Investigational Pharmacy Services

Houston, Texas, 77030, United States

Location

The Second Hospital of Anhui Medical University

Hefei, Anhui, 230601, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Peking University People's Hospital

Beijing, Beijing Municipality, 100144, China

Location

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

Location

Fujian Cancer Hospital

Fuzhou, Fujian, 350015, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guandong, 510000, China

Location

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guandong, 510080, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

Location

Xiangya Hospital, Central South University

Changsha, Huanan, 410008, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

The Affiliated Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

Location

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, 110042, China

Location

The Second Affiliated Hospital of Xi'An Jiaotong University

Xi'an, Shaanxi, 710004, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266003, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 201315, China

Location

Renji Hospital Shanghai Jiaotong University School of Medicine - West Branch

Shanghai, Shanghai Municipality, 201315, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 453000, China

Location

The First Affiliated Hospital of Zhejiang University school of medicine

Hangzhou, Zhejiang, 310003, China

Location

Centre Léon Bérard

Lyon, Rhone, 69373, France

Location

Institut Gustave Roussy

Villejuif, Val de Marne, 94805, France

Location

Asan Medical Center

Seoul, Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, Seoul, 05505, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, Madrid, 28040, Spain

Location

Royal Marsden Hospital-London

London, London, SW36JJ, United Kingdom

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2021
• First Posted: June 23, 2021
• Study Start: August 6, 2021
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); FR (2); ES (2); GB (1); CN (19); KR (2)