NSCLC, Solid Tumor
Conditions
Keywords
KRAS G12C, EGFR
Brief summary
To evaluate the safety and tolerability of JAB-3312 administered in investigational regimens in adult participants with advanced solid tumors.
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.
Interventions
DRUGJAB-3312
JAB-3312 will be administered orally, variable dose.
DRUGBinimetinib
Binimetinib will be administered orally.
DRUGPembrolizumab
Pembrolizumab will be administered as an intravenous infusion.
DRUGSotorasib
Sotorasib will be administered orally.
DRUGOsimertinib
Osimertinib will be administered orally.
Sponsors
AbbVie
Allist Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with dose limiting toxicities | 24 months | 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) |
| Objective response rate (ORR) | 24 months | ORR is defined as the proportion of participants with complete response or partial response (CR+PR). (Dose expansion phase) |
| Duration of response (DOR) | 24 months | 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) |
| Duration of response (DCR) | 24 months | DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD). (Dose expansion phase) |
| Progression-free survival (PFS) | 24 months | 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) |
| Overall survival (OS) | 24 months | 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) |
| Number of participants with adverse events | 24 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration-time curve (AUC) | 24 months | Area under the plasma concentration time curve of JAB-3312(dose escalation phase) |
| Objective response rate (ORR) | 24 months | ORR is defined as the proportion of participants with complete response or partial response (CR+PR). (Dose escalation phase) |
| Number of participants with adverse events | 24 months | 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) |
| Duration of response (DOR) | 24 months | 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) |
| Duration of response (DCR) | 24 months | DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD). (Dose escalation phase) |
| Progression-free survival (PFS) | 24 months | 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) |
| Overall survival (OS) | 24 months | 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) |
| Plasma concentration (Cmax) | 24 months | Highest observed plasma concentration of JAB-3312(dose escalation phase) |
| Time to achieve Cmax (Tmax) | 24 months | Time of highest observed plasma concentration of JAB-3312(dose escalation phase) |
Countries
United States
Outcome results
None listed