This is an open-label, dose-exploration and expansion study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of IMM-1-104 when administered as monotherapy or in combination with approved agents in participants with RAS-mutated or RAS/MAPK activated advanced or metastatic solid tumors. The dose exploration will identify the candidate recommended Phase 2 candidate optimal dose of IMM-1-104 to further explore the anti-tumor activity of IMM-1-104 as monotherapy and in combination with approved agents in multiple Phase 2a proof-of-concept cohorts in malignancies of interest.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
209
Once-daily, oral IMM-1-104 dose administered in 28-day cycles until treatment discontinuation criteria are met
Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of gemcitabine and nab-paclitaxel until treatment discontinuation criteria are met. Gemcitabine will be administered at a dose of 1000 mg/m\^2 nab-Paclitaxel will be administered at a dose of 125 mg/m\^2
Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of modified FOLFIRNOX until treatment discontinuation criteria are met. FOLFIRINOX will be administered as follows: Folinic Acid will be administered at 400 mg/m\^2 Fluorouracil will be administered at 2400 mg/m\^2 Irinotecan will be administered at 150 mg/m\^2 Oxaliplatin will be administered at 85 mg/m\^2
Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with twice daily oral dose of dabrafenib until treatment discontinuation criteria are met. Dabrafenib will be administered at a dose of 150mg daily (75mg twice daily).
Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of pembrolizumab in sequence or concurrently depending on the enrolled cohort (two sub cohorts) until treatment discontinuation criteria are met. Pembrolizumab will be administered at a dose of 400mg.
Mayo Clinic
Scottsdale, Arizona, United States
City of Hope
Duarte, California, United States
University of California San Diego
San Diego, California, United States
Sarcoma Oncology Center
Santa Monica, California, United States
Sarah Cannon Research Institute
Denver, Colorado, United States
Mayo Clinic
Jacksonville, Florida, United States
Florida Cancer Specialists and Research Institute
Lake Mary, Florida, United States
Northwestern University
Chicago, Illinois, United States
University of Chicago
Chicago, Illinois, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
...and 10 more locations
Phase 1: Adverse Events
Number of participants with adverse events
Time frame: From treatment initiation through 30 days following the last IMM-1-104 dose
Phase 1: Dose-Limiting Toxicities
Number of participants with dose-limiting toxicities
Time frame: The first 21 days of study treatment
Phase 1: Recommended Phase 2 Candidate Optimal Dose
Selection of candidate optimal dose to take forward into Ph2a
Time frame: Initiation of study treatment through 21 days (up to approximately 18 months)
Phase 2a: Overall Response Rate
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 (12 cycles) of study treatment
Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104
Cmax
Time frame: After 12 weeks (3 Cycles) of study treatment
Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104
Tmax
Time frame: After 12 weeks (3 Cycles) of study treatment
Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104
AUC0-t
Time frame: After 12 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 16 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
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