Phase 1 (Dose Escalation) of this study will assess the safety, tolerability, dose-limiting toxicity (DLT), and will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of EU101 in participants with advanced solid tumors. Phase 2 (Dose Expansion) of the study will assess the antitumor effect of EU101 in two indications including colorectal cancer (CRC) and non-small cell lung cancer (NSCLC).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
110
EU101 will be administered via intravenous infusion.
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
RECRUITINGMary Crowley Center
Dallas, Texas, United States
RECRUITINGNational Cancer Center
Ilsan, South Korea
NOT_YET_RECRUITINGSamsung Seoul Hospital
Seoul, South Korea
RECRUITINGSeoul Asan
Seoul, South Korea
RECRUITINGSeverance Hospital
Seoul, South Korea
RECRUITINGPhase 1: Number of Participants With Adverse Event (AEs) and Serious Adverse Events (SAEs) and Adverse Events Leading to Discontinuation
Time frame: Baseline up to 30 months
Phase 1: Number of Participants With Dose Limiting Toxicity (DLT)
Time frame: At the end of Cycle 1 (Each cycle is of 21 Days)
Phase 1: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
Laboratory assessments include hematology, serum chemistry, other blood tests, coagulation, and urine analysis. Number of participants with clinically significant abnormalities will be reported.
Time frame: Baseline up to 24 months
Phase 1: Number of Participants With Clinically Significant Abnormalities in Vital Signs
Vital signs will include body temperature, pulse rate, and systolic and diastolic blood pressure measurements. Number of participants with clinically significant abnormalities will be reported.
Time frame: Baseline up to 24 months
Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examination
Physical examination will include head, eyes, ears, nose and throat; heart; lungs; abdomen; skin; cervical and axillary lymph nodes; and neurological and musculoskeletal systems. Number of participants with clinically significant abnormalities will be reported.
Time frame: Baseline up to 24 months
Phase 1: Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG)
ECG parameters included heart rhythm, pulse rate intervals, QRS, QT intervals, RR intervals and corrected QT(QTc) intervals. Number of participants with clinically significant abnormalities will be reported.
Time frame: Baseline up to 24 months
Phase 2: Objective Response Rate (ORR)
Objective response rate (ORR), defined as the percentage of participants with a best overall response (BOR) of either a complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for solid tumors by investigators.
Time frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 24 months)
Phase 1: Objective Response Rate (ORR)
Objective response rate (ORR), defined as the percentage of participants with a BOR of either a complete response (CR) or partial response (PR), per RECIST version 1.1 for solid tumors by investigators.
Time frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 24 months)
Phase 1 and 2: Duration of Response (DOR)
Time frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months)
Phase 1 and 2: Disease Control Rate (DCR)
DCR will be defined similarly to ORR but also including stable disease (SD) in the categorization of response (i.e, RECIST response of either CR, PR, or SD).
Time frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months)
Phase 1 and 2: Time to Response (TTR)
Time frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months)
Phase 1 and 2: Time to Progression (TTP)
Time frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months)
Phase 1 and 2: Durable Clinical Benefit (DCB)
DCB will be defined similarly to DCR but additionally specifying that the disease control be achieved for at least 12 weeks consecutive (i.e, RECIST response of CR, PR or SD for greater than or equal to \[\>=\] 12 weeks consecutive).
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Time frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months)
Phase 1 and 2: Progression-Free Survival (PFS)
Time frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months)
Phase 1 and 2: Overall survival (OS)
Time frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months)
Phase 1 and 2: Maximum Observed Serum Concentration (Cmax) of EU101
Cmax is defined as maximum observed serum concentration.
Time frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)]
Phase 1 and 2: Trough Serum Concentration (Ctrough) of EU101
Ctrough is steady-state pre-dose concentration.
Time frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)]
Phase 1 and 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of EU101
Tmax is defined as time to reach maximum observed serum concentration.
Time frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)]
Phase 1 and 2: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of EU101
AUC0-24 is defined as the area under the serum concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0 to 24).
Time frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)]
Phase 1 and 2: Area Under the Serum Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of EU101
AUC0-last is defined as area under the serum concentration time-curve from time zero to the time of last measured concentration.
Time frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)]
Phase 1 and 2: Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of EU101
AUCinf is defined as area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Time frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)]
Phase 1 and 2: Elimination Half-Life Time (T1/2) of EU101
T1/2 is defined as plasma decay half-life is the time measured for the serum concentration to decrease by one half.
Time frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)]
Phase 1 and 2: Apparent Volume of Distribution (Vd/F) of EU101
Vd/F is defined as volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.
Time frame: Baseline (Day 1)
Phase 1 and 2: Apparent Oral Clearance of (CL/F) of EU101
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time frame: Baseline (Day 1)
Phase 1 and 2: Mean Residence Time (MRT) of EU101
MRT is defined as AUMC(0 - inf) divided by AUC(0 - inf), where AUMC(0 - inf) is the area under the first moment curve from time 0 extrapolated to infinite time.
Time frame: Baseline (Day 1)
Phase 1 and 2: Renal clearance (CLr) of EU101
CLr is defined as renal clearance is the volume of plasma completely cleared of EU101 by the kidneys per unit time.
Time frame: Baseline (Day 1)
Phase 1 and 2: Number of Participants with Positive Antidrug Antibodies (ADA)
The immunogenic potential of EU101 will be assessed by summarizing the number of participants who develop detectable antidrug antibody (ADAs).
Time frame: Baseline up to 56 months
Phase 2: Number of Participants With AEs and SAEs by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: Time from first dose of study treatment up to 30 months