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

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03565003
• Other study ID #: JAB-3068-02
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 20, 2018
• Est. completion date: September 2022

Study information

• Verified date: March 2022
• Source: Jacobio Pharmaceuticals Co., Ltd.
• Contact: Yuankai Shi, MD
• Phone: 86 010 87788293
• Email: syuankaipumc[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: September 2022
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Esophageal Cancer
• Head and Neck Cancer
• Non-small Cell Lung Cancer
• Other Metastatic Solid Tumors

Intervention

Drug:
• JAB-3068
25 mg,100 mg

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Cancer Hospital	Beijing	Beijing
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Chinese PLA Central Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Jacobio Pharmaceuticals Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with dose limiting toxicities	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.	At the end of Cycle 1 (each cycle is 28 days)
Primary	Objective response rate	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	Approximately 2 years
Primary	Duration of response	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	Approximately 2 years
Secondary	Number of participants with adverse events	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	Approximately 2 years
Secondary	Area under the curve	Area under the plasma concentration time curve of JAB-3068	Approximately 2 years
Secondary	Cmax	Highest observed plasma concentration of JAB-3068	Approximately 2 years
Secondary	Tmax	Time of highest observed plasma concentration of JAB-3068	Approximately 2 years
Secondary	T1/2	Half life of JAB-3068	Approximately 2 years
Secondary	Objective response rate	ORR is defined as the proportion of participants with complete response or partial response (CR+PR) in dose escalation.	Approximately 2 years
Secondary	Duration of response	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.	Approximately 2 years