This is a multicenter, open-label, phase I study to evaluate the safety, efficacy, and pharmacokinetic (PK)/pharmacodynamic(PD) characteristics of SIM0237 in participants with advanced solid tumors.
The study starts with a dose escalation part (Part 1) followed by a dose expansion part (Part 2). The main purpose of this study is to evaluate the safety and tolerability of SIM0237 and determine the maximum tolerated dose (MTD) (if any) and/or the recommended dose(s) (RD) and preliminary anti-tumor activity when given once every week or other dosing regimens. Additional purposes of the study are to evaluate the pharmacokinetics (PK) properties, immunogenicity, correlation of the biomarkers and PK profile with anti-tumor activity.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
192
SIM0237 should be administered intravenously at recommended dose qw or other dosing regimens
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, United States
NYU Langone
New York, New York, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Anhui Provincial Hospital
Dose Escalation (Part One): Incidence and nature of Dose-Limiting Toxicity (DLT)
DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for Cytokine Release Syndrome (CRS).
Time frame: 18 months
Dose Escalation (Part One): Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
Time frame: 18 months
Dose Escalation (Part One): Percentage of participants experiencing AE related dose interruptions and dose delays, dose intensity
Occurrence of AE related dose interruptions, dose delays and dose intensity (duration of SIM0237 exposure).
Time frame: 18 months
Dose Expansion (Part Two): Objective Response Rate (ORR)
Proportion of participants who have a confirmed Complete Response (CR) or a Partial Response (PR), as the Best Overall Response (BOR) determined by Investigator per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: 12 months
Dose Expansion (Part Two): Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
Time frame: 18 months
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Hefei, Anhui, China
Fujian Cancer Hospital
Fuzhou, Fujian, China
Henan Cancer Hospital
Zhengzhou, Henan, China
Hunan Cancer Hospital
Changsha, Hunan, China
Shandong Cancer Hospital
Jinan, Shandong, China
The First Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Dose Expansion (Part Two): Percentage of participants experiencing AE related dose interruptions and dose delays, dose intensity
Occurrence of AE related dose interruptions, dose delays and dose intensity (duration of SIM0237 exposure).
Time frame: 18 months
Dose Escalation and Expansion: Assessment of SIM0237 Cmax
Maximum concentration observed (Cmax) observed from the PK profile
Time frame: 30 months
Dose Escalation and Expansion: Assessment of SIM0237 AUC
Area under the concentration versus time curve calculated using the trapezoidal method
Time frame: 30 months
Dose Escalation and Expansion: Assessment of SIM0237 T1/2
The time it takes for half the drug concentration to be eliminated calculated using slope of the terminal line
Time frame: 30 months
Dose Escalation and Expansion: Assessment of SIM0237 antibody (ADA)
Incidence, duration, titer of serum anti-SIM0237 ADA
Time frame: 30 months
Dose Escalation (Part One): Objective Response Rate (ORR)
Proportion of participants who have a confirmed complete response (CR) or a Partial Response (PR), as the Best Overall Response (BOR) determined by Investigator per the RECIST v1.1
Time frame: 48 months
Dose Escalation and Expansion: Duration Of Response (DOR) assessed by investigator per RECIST Version 1.1
DOR is defined as the time from the measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease.
Time frame: 48 months
Dose Escalation and Expansion: Disease Control Rate (DCR) assessed by investigator per RECIST Version 1.1
Disease Control Rate is defined as the percentage of participants who have achieved CR or PR or have demonstrated stable disease
Time frame: 48 months
Dose Escalation and Expansion: Progression-Free Survival (PFS) assessed by investigator per RECIST Version 1.1
PFS is defined as the time from the date of first administration of SIM0237 to the date of the first documented disease progression determined by Investigator as per RECIST 1.1 or death from any cause, whichever occurs first
Time frame: 48 months
Dose Escalation and Expansion: Time-To-Progression (TTP) assessed by investigator per RECIST Version 1.1
TTP is defined as the time from the date of first administration of SIM0237 to the date of the first documented disease progression
Time frame: 48 months
Dose Escalation and Expansion: Overall Survival (OS)
Overall Survival is defined as the time from the date of first administration of SIM0237 to death due to any cause
Time frame: 48 months
Dose Escalation and Expansion: ORR in participants with different PD-LI expression levels
ORR is defined as proportion of participants who have a confirmed Complete Response (CR) or a Partial Response (PR), as the Best Overall Response (BOR) determined by Investigator per RECIST v1.1. PD-L1 expression will be tested using 22C3 IHC and scored using TPS and/or CPS algorithm.
Time frame: 48 months