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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Solid Tumor, NSCLC

Intervention / Treatment
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* Drug: JAB-3312
* Drug: Binimetinib
* Drug: Pembrolizumab
* Drug: Sotorasib
* Drug: Osimertinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KRAS G12C, EGFR