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
Overview
- Phase
- Phase 1
- Enrollment
- 120
- Locations
- 4
- Primary Endpoint
- Number of participants with dose limiting toxicities
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent obtained prior to any study-related procedure being performed;
- •Age 18 years or older;
- •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;
- •Patients with life expectancy ≥3 months;
- •Dose expansion(phase IIa ): patients have available archival tissue can be provided or willing to perform biopsy to provide fresh tumor tissue.
- •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;
- •Eastern Cooperative Oncology Group performance score 0 or 1;
- •Patients who have sufficient baseline organ function.
Exclusion Criteria
- •Patients with life-threatening autoimmune disease or with autoimmune disorder and who are on long-term steroid treatment;
- •History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO;
- •Lymphoma with brain metastasis; Other solid tumors:Known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases;
- •Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
- •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
- •Patients who have impaired cardiac function or clinically significant cardiac diseases
- •Use of anti-cancer treatment drug ≤21 days prior to the first dose of JAB-
- •Use of an investigational drug during the past 30 days prior to the first dose of JAB-3068.
Arms & Interventions
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.
Intervention: JAB-3068 (Drug)
Outcomes
Primary Outcomes
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.
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
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 Outcomes
- Cmax(Approximately 2 years)
- Objective response rate(Approximately 2 years)
- Area under the curve(Approximately 2 years)
- Duration of response(Approximately 2 years)
- T1/2(Approximately 2 years)
- Tmax(Approximately 2 years)
- Number of participants with adverse events(Approximately 2 years)