This is a FIH, ascending dose study to characterize the safety, tolerability, optimal dose and preliminary anti-tumor activity of IMM-6-415 in participants with advanced or metastatic solid tumors harboring RAS or RAF oncogenic mutations.
The dose exploration will identify the candidate recommended Phase 2 dose (RP2D) of IMM-6-415 to further explore the anti-tumor activity of IMM-6-415 as monotherapy in Phase 2a tumor-specific cohorts. Patients will be self-administering IMM-6-415 on a daily basis for up to 16 cycles (21-day cycles). During the first 2 cycles, PK and PD will be assessed. Solid tumor types with RAS/RAF mutations are eligible.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Twice daily, oral tablet administered in 21-day cycles until treatment discontinuation criteria are met.
Honor Health Research Institute
Scottsdale, Arizona, United States
City of Hope
Duarte, California, United States
Sarah Cannon Research Institute
Denver, Colorado, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Phase 1/2a: Adverse Events
Number of participants with adverse events
Time frame: From treatment initiation through 30 days following the last IMM-6-415 dose
Phase 1: Dose-Limiting Toxicities (DLT)
Number of participants with dose-limiting toxicities
Time frame: The first 21 days of study treatment
Phase 1: Recommended Phase 2 Dose (RP2D) candidate
Selection of candidate RP2D to take forward into Ph2a
Time frame: Initiation of study treatment through 21 days (up to approximately 18 months)
Phase 1: Maximum Observed Plasma Concentration of IMM-6-415
Cmax
Time frame: After 9 weeks (3 Cycles) of study treatment
Phase 1: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415
Tmax
Time frame: After 9 weeks (3 Cycles) of study treatment
Phase 1: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415
AUC0-t
Time frame: After 9 weeks (3 Cycles) of study treatment
Phase 1: Pharmacodynamic (PD) Activity of IMM-6-415 Plasma Concentrations Over Time
Surrogate PD Biomarker Assay, pERK
Time frame: After 9 weeks (3 Cycles) of study treatment
Phase 2a: Overall Response Rate (ORR)
The proportion of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR), based on RECIST 1.1 criteria
Time frame: After up to 48 weeks (16 cycles) of study treatment
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MD Anderson Cancer Center
Houston, Texas, United States
Phase 2a: Maximum Observed Plasma Concentration of IMM-6-415
Cmax
Time frame: After 9 weeks (3 Cycles) of study treatment
Phase 2a: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415
Tmax
Time frame: After 9 weeks (3 Cycles) of study treatment
Phase 2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415
AUC0-t
Time frame: After 9 weeks (3 Cycles) of study treatment
Phase 2a: Disease Control Rate (DCR)
The proportion of participants who have a best overall response (BOR) of stable disease (SD) or better
Time frame: After 12 weeks (4 Cycles) of study treatment
Phase 2a: Progression Free Survival (PFS)
The time interval between study treatment start and disease progression or death due to any cause.
Time frame: Up to approximately 2 years
Phase 2a: Duration of Response (DOR)
The time interval between an assessment of partial response (PR) or better and disease progression or death due to any cause.
Time frame: Up to approximately 2 years
Phase 2a: Landmark 3-Month Survival
The proportion of participants who are still alive after three months on study
Time frame: After 3 months of study participation.
Phase 2a: Landmark 6-Month Survival
The proportion of participants who are still alive after six months on study
Time frame: After 6 months of study participation
Phase 2a: Overall Survival (OS)
The time interval between study treatment start and death due to any cause
Time frame: Up to approximately 2 Years