Clinical trial NCT03565003: A First-in-Human Study of JAB-3068 (SHP2 Inhibitor) in Adult Patients With Advanced Solid Tumors in China
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Head and Neck Cancer
Esophageal Cancer
Other Metastatic Solid Tumors
Keywords: JAB-3068
SHP2
PTPN11
ESCC
NSCLC
HNSCC
Colorectal cancer (CRC)
EGFR
Lead sponsor: Jacobio Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-06-21
Enrollment: 126
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 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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of participants with dose limiting toxicities
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Objective response rate
timeFrame: Approximately 2 years
measure: Duration of response
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: Approximately 2 years
measure: Area under the curve
timeFrame: Approximately 2 years
measure: Cmax
timeFrame: Approximately 2 years
measure: Tmax
timeFrame: Approximately 2 years
measure: T1/2
timeFrame: Approximately 2 years
measure: Objective response rate
timeFrame: Approximately 2 years
measure: Duration of response
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese PLA Central Hospital
state: Beijing
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Yuankai Shi, MD
role: STUDY_CHAIR
References: