A Study of NB003 in Patients With Advanced Malignancies

Advanced Solid Tumor Clinical Trial

Official title:

A Multicenter Phase 1, Open-Label Study of NB003 to Assess Safety, Tolerability, Pharmacokinetics and Efficacy in Patients With Advanced Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04936178
• Other study ID #: NB003-01
• Status: Recruiting
• Phase: Phase 1
• Start date: August 6, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: Ningbo Newbay Technology Development Co., Ltd
• Contact: Lanjiao Wu
• Phone: +86 13761453966
• Email: TMF-ISF[@]newbaypharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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), and the RP2D and a dose expansion phase to further explore the safety, PK and efficacy of NB003.

The dose escalation phase will enroll patients with advanced gastrointestinal stromal tumor (GIST) who have progressed on or had an intolerability to imatinib and other standard of cares (SoCs) or refused other SoCs, and patients with advanced malignancies other than GIST that harbors KIT or PDGFRα gene alterations who have relapsed or have refractory disease without an available effective therapy. The number of patients to be enrolled during the dose escalation part will vary depending on the underlining dose-toxicity curve and the number of dose levels tested prior to reaching MTD or MAD. After the MTD or MAD has been determined, based on emerging safety/PK data, one or more putative RP2D(s) will be explored in dose escalation phase with approximately 15 patients for each provisional RP2D(s) to establish the RP2D for dose expansion phase. This step will be regarded as RP2D confirmation part of dose escalation phase.

In the dose expansion phase, additional patients will be enrolled 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. Dose expansion phase is planned to investigate NB003 at the RP2D determined from dose escalation phase.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 258
• Est. completion date: December 31, 2025
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males or females of any race =18 years age.

2. Histologically-confirmed diagnosis of unresectable, relapsed or metastatic GIST or other advanced malignancies.

1. 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 PDGFRa gene alterations (central laboratory confirmation is not required for screening).

2. For dose expansion phase:

Cohort 1: GIST patients with KIT or PDGFRa 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 PDGFRa 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 PDGFRa 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 PDGFRa 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 PDGFRa 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 PDGFRa gene alterations.

3. For dose expansion phase: at least one measurable lesion per RECIST v1.1/mRECIST.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

5. Life expectancy = 12 weeks.

6. Adequate organ and marrow function.

7. Tumor sample collection is required.

Exclusion Criteria:

1. 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.

2. Major surgery within 4 weeks of the first dose.

3. Radiotherapy with a limited field of radiation for palliation within 1 week prior to the first dose, with the exception as defined.

4. Patients currently receiving medications or herbal supplements known to be strong inhibitors or inducers of CYP3A4.

5. Patients currently receiving acid-reducing agents and are unable to stop use at least 2 weeks prior to the first dose.

6. Any known active central nervous system metastases and/or carcinomatous meningitis. Active infection including hepatitis B, hepatitis C, and HIV.

7. 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.

8. 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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• NB003 tablets
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.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Cancer Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	Xiangya Hospital, Central South University	Changsha	Huanan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Sun Yat-sen University Cancer Center	Guangzhou	Guandong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guandong
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guandong
China	Harbin Medical University Cancer Hospital	Ha'erbin	Heilongjiang
China	The First Affiliated Hospital of Zhejiang University school of medicine	Hangzhou	Zhejiang
China	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Renji Hospital Shanghai Jiaotong University School of Medicine - West Branch	Shanghai	Shanghai
China	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	The 2nd Hospital of Xi'An Jiaotong University	Xi'an	Shanxi
France	Centre Léon Bérard	Lyon cedex 08	Rhone
France	Institut Gustave Roussy	Villejuif cedex	Val De Marne
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
United Kingdom	Royal Marsden Hospital-London	London
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	U T MD Anderson Cancer Center Investigational Pharmacy Services	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	Memorial Sloan Kettering Cancer Center	Long Island City	New York
United States	Oregon Health & Science University (OHSU)	Portland	Oregon
United States	Standford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Ningbo Newbay Technology Development Co., Ltd

Countries where clinical trial is conducted

United States,  China,  France,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cancer relevant gene mutations	Dose Escalation Phase and Dose Expansion Phase:Cancer relevant gene mutations	Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled
Primary	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
Primary	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
Primary	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
Primary	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	Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t)	Dose Escalation Phase and Dose Expansion Phase: AUC (0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to the time of the last measurable concentration.	Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled
Secondary	Maximum observed plasma concentration (Cmax)	Dose Escalation Phase and Dose Expansion Phase: Maximum observed plasma concentration (Cmax)	Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled
Secondary	Time to Cmax (Tmax)	Dose Escalation Phase and Dose Expansion Phase: Time to Cmax (Tmax)	Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled
Secondary	Terminal elimination half life	Dose Escalation Phase and Dose Expansion Phase: Terminal elimination half life	Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled
Secondary	Objective Response Rate (ORR)	Dose Escalation 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 24 months since the escalation first subject enrolled
Secondary	Duration of Response(DOR)	Dose Escalation 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 24 months since the escalation first subject enrolled