JAB-3312 Based Combination Therapy in Adult Patients With Advanced Solid Tumors

A Phase 1/2a, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-3312 Based Combination Therapies in Adult Patients With Advanced Solid Tumors

To evaluate the safety and tolerability of JAB-3312 administered in investigational regimens in adult participants with advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: NSCLC; Solid Tumor
• Intervention / Treatment: Drug: JAB-3312; Drug: Pembrolizumab; Drug: Binimetinib; Drug: Sotorasib; Drug: Osimertinib

Detailed Description

To assess the safety and tolerability and determine the Recommended phase 2 dose (RP2D) of JAB-3312 in combination with PD1 inhibitor or MEK inhibitor in patients with advanced solid tumors.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jacobio Pharmaceuticals; Phone Number: 86 10 56315466; Email: clinicaltrials@jacobiopharma.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Research Site
    • Scottsdale, Arizona, United States, 85259
      • Not yet recruiting
      • Research Site
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Research Site
    • Orange City, Florida, United States, 32763
      • Recruiting
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Recruiting
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Recruiting
      • Research Site
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must have histologically or cytologically confirmed metastatic or locally advanced solid tumor. Some cohorts must meet specific expression or gene mutation where indicated
• Sufficient organ function
• Participants must have at least 1 measurable lesion as defined by RECIST v1.1
• Must be able to provide an archived tumor sample
• ECOG performance status score of 0 or 1.

Exclusion Criteria:

• History of cancer that is histologically distinct from the cancers under study
• Active or untreated central nervous system (CNS) metastases
• History of pneumonitis or interstitial lung disease (ILD)
• Has active hepatitis B, hepatitis C infection, HIV
• Any severe and/or uncontrolled medical conditions
• LVEF ≤50%
• QTcF >470 msec

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JAB-3312+Pembrolizumab dose escalation; Dose escalation	Drug: JAB-3312; JAB-3312 will be administered orally, variable dose.; Drug: Pembrolizumab; Pembrolizumab will be administered as an intravenous infusion.
Experimental: JAB-3312+ Binimetinib dose escalation; Dose escalation	Drug: JAB-3312; JAB-3312 will be administered orally, variable dose.; Drug: Binimetinib; Binimetinib will be administered orally.
Experimental: JAB-3312+Pembrolizumab dose expansion; Dose expansion	Drug: JAB-3312; JAB-3312 will be administered orally, variable dose.; Drug: Pembrolizumab; Pembrolizumab will be administered as an intravenous infusion.
Experimental: JAB-3312+Binimetinib dose expansion; Dose expansion	Drug: JAB-3312; JAB-3312 will be administered orally, variable dose.; Drug: Binimetinib; Binimetinib will be administered orally.
Experimental: JAB-3312+Sotorasib dose escalation; Dose escalation	Drug: JAB-3312; JAB-3312 will be administered orally, variable dose.; Drug: Sotorasib; Sotorasib will be administered orally.
Experimental: JAB-3312+ Osimertinib dose escalation; Dose escalation	Drug: JAB-3312; JAB-3312 will be administered orally, variable dose.; Drug: Osimertinib; Osimertinib will be administered orally.
Experimental: JAB-3312+ Sotorasib dose expansion; Dose expansion	Drug: JAB-3312; JAB-3312 will be administered orally, variable dose.; Drug: Sotorasib; Sotorasib will be administered orally.
Experimental: JAB-3312+ Osimertinib dose expansion; Dose expansion	Drug: JAB-3312; JAB-3312 will be administered orally, variable dose.; Drug: Osimertinib; Osimertinib will be administered orally.

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. (Dose escalation phase)	24 months
Objective response rate (ORR)	ORR is defined as the proportion of participants with complete response or partial response (CR+PR). (Dose expansion phase)	24 months
Duration of response (DOR)	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. (Dose expansion phase)	24 months
Duration of response (DCR)	DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD). (Dose expansion phase)	24 months
Progression-free survival (PFS)	PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression or death which occurs first. (Dose expansion phase)	24 months
Overall survival (OS)	OS is defined as the interval of time between the date of first treatment until death, loss to follow up or termination of the study by the sponsor. (Dose expansion phase)	24 months
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 (Dose escalation phase)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression or death which occurs first. (Dose escalation phase)	24 months
Overall survival (OS)	OS is defined as the interval of time between the date of first treatment until death, loss to follow up or termination of the study by the sponsor(Dose escalation phase)	24 months
Objective response rate (ORR)	ORR is defined as the proportion of participants with complete response or partial response (CR+PR). (Dose escalation phase)	24 months
Duration of response (DOR)	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. (Dose escalation phase)	24 months
Duration of response (DCR)	DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD). (Dose escalation phase)	24 months
Plasma concentration (Cmax)	Highest observed plasma concentration of JAB-3312(dose escalation phase)	24 months
Time to achieve Cmax (Tmax)	Time of highest observed plasma concentration of JAB-3312(dose escalation phase)	24 months
Area under the plasma concentration-time curve (AUC)	Area under the plasma concentration time curve of JAB-3312(dose escalation phase)	24 months
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 (Dose expansion phase)	24 months

Collaborators and Investigators

• Sponsor: Jacobio Pharmaceuticals Co., Ltd.
• Collaborators: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2021
• Primary Completion (Anticipated): January 5, 2024
• Study Completion (Anticipated): February 5, 2024

Study Registration Dates

• First Submitted: January 18, 2021
• First Submitted That Met QC Criteria: January 21, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: KRAS G12C, EGFR
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Osimertinib; Pembrolizumab
• Other Study ID Numbers: JAB-3312-1003

Drug and device information, study documents

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