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A First-in-Human Study of JAB-3068 (SHP2 Inhibitor) in Adult Patients With Advanced Solid Tumors in China

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ClinicalTrials.gov Identifier: NCT03565003
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : August 6, 2020
Sponsor:
Information provided by (Responsible Party):
Jacobio Pharmaceuticals Co., Ltd.

Brief Summary:
This is a Phase 1/2a, open-label, multi-center study of JAB-3068 in Patients with advanced solid tumors.This study has two phases: dose escalation phase and dose expansion phase.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Head and Neck Cancer Esophageal Cancer Other Metastatic Solid Tumors Drug: JAB-3068 Phase 1 Phase 2

Detailed Description:

Dose escalation study phase is designed to determine the maximum tolerated dose (MTD) according to a 3+3 design and recommended phase II dose (RP2D) and to characterize the safety, tolerability, and pharmacokinetics (PK) profile of JAB-3068. Other dose regimens may be explored based on the analysis of emerging PK and safety data. at this study phase, JAB-3068 dministered orally once daily (QD) or twice daily (BID) or once every other day (QOD) in 28-day treatment cycles to adult patients with advanced solid tumors,

Dose expansion study phase is designed to evaluate the antitumor activity(ORR and DOR) of JAB-3068 in patients with NSCLC, ESCC and HNSCC.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a, Multi-Center, Dose Escalation/Dose Expansion, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-3068 in Adult Patients With Advanced Solid Tumors
Actual Study Start Date : November 20, 2018
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: JAB-3068 (SHP2 inhibitor)
JAB-3068 will be administered orally in the morning following a fast of approximately 6 hours before on PK collection. Patients will continue to fast for approximately 2 hours after the administration of JAB-3068. On non-PK days patients will fast approximately 2 hours before JAB-3068 and continue to fast for approximately 2 hours afterwards.
Drug: JAB-3068
25 mg,100 mg




Primary Outcome Measures :
  1. Number of participants with dose limiting toxicities [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
    Number of participants with dose limiting toxicities (DLTs) in the dose escalation phase. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle with JAB-3068.

  2. Objective response rate [ Time Frame: Approximately 2 years ]
    ORR is defined as the proportion of participants with complete response or partial. the ORR of JAB-3068 in patients with ESCC, NSCLC and HNSCC will be evaluated separately in dose expansion

  3. Duration of response [ Time Frame: Approximately 2 years ]
    DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first. The DOR of JAB-3068 in patients with ESCC, NSCLC and HNSCC will be evaluated separately in dose expansion


Secondary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: Approximately 2 years ]
    All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imaging and ophthalmological assessments

  2. Area under the curve [ Time Frame: Approximately 2 years ]
    Area under the plasma concentration time curve of JAB-3068

  3. Cmax [ Time Frame: Approximately 2 years ]
    Highest observed plasma concentration of JAB-3068

  4. Tmax [ Time Frame: Approximately 2 years ]
    Time of highest observed plasma concentration of JAB-3068

  5. T1/2 [ Time Frame: Approximately 2 years ]
    Half life of JAB-3068

  6. Objective response rate [ Time Frame: Approximately 2 years ]
    ORR is defined as the proportion of participants with complete response or partial response (CR+PR) in dose escalation.

  7. Duration of response [ Time Frame: Approximately 2 years ]
    DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first in dose escalation.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent obtained prior to any study-related procedure being performed;
  2. Age 18 years or older;
  3. Dose escalation(phase I): Patients with histologically or cytologically confirmed, advanced solid tumors (including lymphoma) which have progressed from standard therapy or for whom no standard therapy exists; Dose expansion(phase IIa ): Patients with histologically or cytologically confirmed, advanced NSCLC, ESCC, HNSCC which have progressed from standard therapy;
  4. Patients with life expectancy ≥3 months;
  5. Dose expansion(phase IIa ): patients have available archival tissue can be provided or willing to perform biopsy to provide fresh tumor tissue.
  6. Patients with other solid tumors must have at least one measurable lesion as defined by RECIST v1.1;Patients with Lymphomas must have at least one measurable lesion as defined by IWG 2007 criteria;
  7. Eastern Cooperative Oncology Group performance score 0 or 1;
  8. Patients who have sufficient baseline organ function.

Exclusion Criteria:

  1. Patients with life-threatening autoimmune disease or with autoimmune disorder and who are on long-term steroid treatment;
  2. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO;
  3. Lymphoma with brain metastasis; Other solid tumors:Known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases;
  4. Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
  5. Patients who have any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the Investigator and Sponsor, could affect the patient's participation in the study
  6. Patients who have impaired cardiac function or clinically significant cardiac diseases
  7. Use of anti-cancer treatment drug ≤21 days prior to the first dose of JAB-3068.
  8. Use of an investigational drug during the past 30 days prior to the first dose of JAB-3068.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03565003


Contacts
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Contact: Yuankai Shi, MD 86 010 87788293 syuankaipumc@126.com

Locations
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China, Beijing
Cancer Hospital, Chinese Academy of Medical Sciences Recruiting
Beijing, Beijing, China, 100021
Contact: Yuankai Shi, MD         
Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China, 100032
Contact: Chunmei Bai, MD         
Principal Investigator: Chunmei Bai, MD         
Beijing Cancer Hospital Recruiting
Beijing, Beijing, China, 100142
Contact: Jian Fang, MD         
Beijing Cancer Hospital Recruiting
Beijing, Beijing, China, 100142
Contact: Lin Shen, MD         
Chinese PLA Central Hospital Recruiting
Beijing, Beijing, China, 100853
Contact: Weiwei Shi, MD         
Sponsors and Collaborators
Jacobio Pharmaceuticals Co., Ltd.
Investigators
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Study Chair: Yuankai Shi, MD Cancer Institute and Hospital, Chinese Academy of Medical Sciences
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Responsible Party: Jacobio Pharmaceuticals Co., Ltd.
ClinicalTrials.gov Identifier: NCT03565003    
Other Study ID Numbers: JAB-3068-02
First Posted: June 21, 2018    Key Record Dates
Last Update Posted: August 6, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jacobio Pharmaceuticals Co., Ltd.:
JAB-3068
SHP2
PTPN11
ESCC
NSCLC
HNSCC
Colorectal cancer (CRC)
EGFR