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
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Allist Pharmaceuticals, Inc.
- Enrollment
- 58
- Locations
- 1
- Primary Endpoint
- Number of participants with adverse events
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
JAB-3312+Pembrolizumab dose escalation
Dose escalation
Intervention: JAB-3312 (Drug)
JAB-3312+Pembrolizumab dose escalation
Dose escalation
Intervention: Pembrolizumab (Drug)
JAB-3312+ Binimetinib dose escalation
Dose escalation
Intervention: JAB-3312 (Drug)
JAB-3312+ Binimetinib dose escalation
Dose escalation
Intervention: Binimetinib (Drug)
JAB-3312+Pembrolizumab dose expansion
Dose expansion
Intervention: JAB-3312 (Drug)
JAB-3312+Pembrolizumab dose expansion
Dose expansion
Intervention: Pembrolizumab (Drug)
JAB-3312+Binimetinib dose expansion
Dose expansion
Intervention: JAB-3312 (Drug)
JAB-3312+Binimetinib dose expansion
Dose expansion
Intervention: Binimetinib (Drug)
JAB-3312+Sotorasib dose escalation
Dose escalation
Intervention: JAB-3312 (Drug)
JAB-3312+Sotorasib dose escalation
Dose escalation
Intervention: Sotorasib (Drug)
JAB-3312+ Osimertinib dose escalation
Dose escalation
Intervention: JAB-3312 (Drug)
JAB-3312+ Osimertinib dose escalation
Dose escalation
Intervention: Osimertinib (Drug)
JAB-3312+ Sotorasib dose expansion
Dose expansion
Intervention: JAB-3312 (Drug)
JAB-3312+ Sotorasib dose expansion
Dose expansion
Intervention: Sotorasib (Drug)
JAB-3312+ Osimertinib dose expansion
Dose expansion
Intervention: JAB-3312 (Drug)
JAB-3312+ Osimertinib dose expansion
Dose expansion
Intervention: Osimertinib (Drug)
Outcomes
Primary Outcomes
Number of participants with adverse events
Time Frame: 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)
Objective response rate (ORR)
Time Frame: 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)
Time Frame: 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)
Progression-free survival (PFS)
Time Frame: 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)
Time Frame: 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 dose limiting toxicities
Time Frame: 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)
Duration of response (DCR)
Time Frame: 24 months
DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD). (Dose expansion phase)
Secondary Outcomes
- Duration of response (DOR)(24 months)
- Number of participants with adverse events(24 months)
- Objective response rate (ORR)(24 months)
- Duration of response (DCR)(24 months)
- Progression-free survival (PFS)(24 months)
- Overall survival (OS)(24 months)
- Area under the plasma concentration-time curve (AUC)(24 months)
- Plasma concentration (Cmax)(24 months)
- Time to achieve Cmax (Tmax)(24 months)