Clinical trial NCT04936178: A Study of NB003 in Patients With Advanced Malignancies
Official title: A Multicenter Phase 1, Open-Label Study of NB003 to Assess Safety, Tolerability, Pharmacokinetics and Efficacy in Patients With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Ningbo Newbay Technology Development Co., Ltd
Sponsor class: INDUSTRY
First posted: 2021-06-23
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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 PDGFRα gene alterations (central laboratory confirmation is not required for screening).
   2. 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.
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.

Primary outcomes:
measure: Incidence of dose-limiting toxicities
timeFrame: Approximately 24 months since the escalation first subject enrolled
measure: Incidence of adverse events
timeFrame: Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled
measure: Objective Response Rate (ORR)
timeFrame: Approximately 26 months since the Expansion first subject enrolled
measure: Duration of Response(DOR)
timeFrame: Approximately 26 months since the Expansion first subject enrolled.
Secondary outcomes:
measure: Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t)
timeFrame: Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled
measure: Time to Cmax (Tmax)
timeFrame: Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled
measure: Terminal elimination half life
timeFrame: Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled
measure: Objective Response Rate (ORR)
timeFrame: Approximately 24 months since the escalation first subject enrolled
measure: Duration of Response(DOR)
timeFrame: Approximately 24 months since the escalation first subject enrolled
Other outcomes:
measure: Cancer relevant gene mutations
timeFrame: Approximately 24 months since the escalation first subject enrolled; Approximately 26 months since the Expansion first subject enrolled
Locations:
city: Stanford
country: United States
facility: Standford University
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Long Island
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Houston
country: United States
facility: U T MD Anderson Cancer Center Investigational Pharmacy Services
state: Texas
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: guandong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: guandong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: guandong
city: Ha'erbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
state: Huanan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Nanjing
country: China
facility: The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'An Jiaotong University
state: Shaanxi
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong University School of Medicine - West Branch
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University school of medicine
state: Zhejiang
city: Lyon cedex 08
country: France
facility: Centre Léon Bérard
state: Rhone
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
state: Val de Marne
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: London
country: United Kingdom
facility: Royal Marsden Hospital-London
Study officials:
References: