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

A Phase 1, Multi-Center, Dose Escalation, 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, multi-center, dose escalation, open-label study to evaluate the safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity of JAB-3068 in adult patients with advanced solid.

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

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80202
      • Recruiting
      • HealthONE Clinic Services Oncology-Hematology
      • Contact: Kelly Mozzetta; Phone Number: 720-754-4646; Email: Kelly.Mozzetta@sarahcannon.com
      • Principal Investigator: Gerald S Falchook, MD
  • Florida
    • Sarasota, Florida, United States, 37203
      • Recruiting
      • Florida Cancer Specialists
      • Contact: Katie Hanchey; Phone Number: 941-377-9993; Email: KHanchey@flcancer.com
      • Principal Investigator: Judy Wang, M.D.
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
      • Contact: Kayla Karan
      • Contact: Kayla Karan; Phone Number: (615)3296815; Email: Kayla.Karan@SarahCannon.com
      • Principal Investigator: Todd M Bauer, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas M. D. Anderson Cancer Center
      • Contact: Sarina A. Piha-Paul, MD
      • Principal Investigator: Sarina A. Piha-Paul, 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. Patients with histologically or cytologically confirmed, advanced solid tumors which have progressed despite standard therapy or for whom no standard therapy exists;
4. Patients with life expectancy ≥3 months;
5. Patients must have at least one measurable lesion as defined by RECIST v1.1;
6. Eastern Cooperative Oncology Group performance score 0 or 1;
7. 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. 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 or 5 half-lives (whichever is shorter) prior to the first dose of JAB-3068;
8. Use of an investigational drug during the past 30 days or 5 half-lives (whichever is shorter) prior to the first dose of JAB-3068;
9. No other anti-cancer therapy (chemotherapy, immunotherapy, hormonal therapy radiotherapy (except for palliative local radiotherapy), biological therapy or other novel agent is to be permitted while the patient is receiving study medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JAB-3068 (SHP2 inhibitor); Daily oral administration of JAB-3068	Drug: JAB-3068; JAB-3068 will be orally administered on a daily basis. Patients need to fast 2 hours before （6 hours for PK days) and 2 hours after each dosing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with dose limiting toxicities	Incidence of 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.	up to 28-day per cycle

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
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.	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)	Approximately 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
pERK	On treatment versus baseline comparison of pharmacodynamic marker pERK (Phosphorylated form of Extracellular signal-regulated kinase) on newly obtained tumor biopsy samples by IHC.	Approximately 2 years

Collaborators and Investigators

• Sponsor: Jacobio Pharmaceuticals Co., Ltd.
• Investigators: Study Director: Jacobio Pharmaceuticals, Jacobio Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2018
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: April 6, 2018
• First Submitted That Met QC Criteria: May 4, 2018
• First Posted (Actual): May 8, 2018

Study Record Updates

• Last Update Posted (Actual): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: NSCLC; Colorectal cancer; EGFR; HNSCC; SHP2; advanced solid tumor; ESCC; PTPN11; JAB-3068
• Other Study ID Numbers: JAB-3068-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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