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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Esophageal Cancer; Non-small Cell Lung Cancer; Other Metastatic Solid Tumors
• Intervention / Treatment: Drug: JAB-3068

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 Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100032
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Chunmei Bai, MD
      • Principal Investigator: Chunmei Bai, MD
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital, Chinese Academy of Medical Sciences
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Chinese PLA Central Hospital
      • Contact: Weiwei Shi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Area under the curve	Area under the plasma concentration time curve of JAB-3068	Approximately 2 years
Cmax	Highest observed plasma concentration of JAB-3068	Approximately 2 years
Tmax	Time of highest observed plasma concentration of JAB-3068	Approximately 2 years
T1/2	Half life of JAB-3068	Approximately 2 years
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
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

Collaborators and Investigators

• Sponsor: Jacobio Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 20, 2018
• Primary Completion (ANTICIPATED): July 1, 2022
• Study Completion (ANTICIPATED): September 1, 2022

Study Registration Dates

• First Submitted: May 29, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (ACTUAL): June 21, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 14, 2022
• Last Update Submitted That Met QC Criteria: March 11, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: NSCLC; EGFR; HNSCC; SHP2; ESCC; PTPN11; Colorectal cancer (CRC); JAB-3068
• Other Study ID Numbers: JAB-3068-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No